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NLM database Documents
Record 1 from database: MEDLINE
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- Title
- Metabolism of dimethyl sulfide, dimethyl sulfoxide, and
dimethyl sulfone in the rabbit.
- Author
- Williams KI; Burstein SH; Layne DS
- Address
-
- Source
- Arch Biochem Biophys, 1966 Oct, 117:1, 84-7
- Abstract
- Abstract unavailable online.
- Language of Publication
- English
- Unique Identifier
- 67181631
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- MeSH Heading (Major)
- Dimethyl Sulfoxide|*ME; Sulfides|*ME; Sulfones|*UR
- MeSH Heading
- Animal; Carbon Isotopes; Chromatography, Gas; Rabbits
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-9861
- Country of Publication
- UNITED STATES
Record 2 from database: MEDLINE
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- Title
- A new method for assay of radioactive dimethyl sulfoxide
and its metabolite, dimethyl sulfone.
- Author
- Hucker HB; Hoffman EA
- Address
-
- Source
- Experientia, 1966 Dec, 22:12, 855-6
- Abstract
- Abstract unavailable online.
- Language of Publication
- English
- Unique Identifier
- 67202189
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- MeSH Heading (Major)
- Dimethyl Sulfoxide|*AN; Sulfones|*AN
- MeSH Heading
- Animal; Chlorides; Rats; Sulfur Isotopes; Tin
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0014-4754
- Country of Publication
- SWITZERLAND
Record 3 from database: MEDLINE
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- Title
- [Effect of dimethyl sulfoxide and dimethyl sulfone on a
destructive process in the joints of mice with spontaneous
arthritis]
- Author
- Muravev IuV; Venikova MS; Pleskovskaia GN; Riazantseva TA;
Sigidin IaA
- Address
-
- Source
- Patol Fiziol Eksp Ter, 1991 Mar, :2, 37-9
- Abstract
- The authors used the blind method for evaluation of the
morphological picture of the joints and the level of
circulating immune complexes to study the effect of
prolonged oral administration of dimethyl sulfoxide (DMSO)
and its main metabolite dimethyl sulfone on the development
of spontaneous arthritis in 36 Mrl/Mn/lnr female mice. It
was found that DMSO and dimethyl sulfone lessen the
destructive changes in the joints, while DMSO also inhibits
the manifestation of immune disorders, i. e. produces a
"basal" effect on the course of spontaneous
chronic arthritis in experimental animals.
- Language of Publication
- Russian
- Unique Identifier
- 91351749
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- MeSH Heading (Major)
- Arthritis|*DT/ET/PA; Dimethyl Sulfoxide|*TU; Sulfones|*TU
- MeSH Heading
- Animal; English Abstract; Female; Mice
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0031-2991
- Country of Publication
- USSR
Record 4 from database: MEDLINE
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- Title
- Ineffectiveness of dimethyl sulfone as a cryoprotectire
agent.
- Author
- Connor KW; Ashwood Smith MJ
- Address
-
- Source
- Cryobiology, 1973 Apr, 10:1, 87-8
- Abstract
- Abstract unavailable online.
- Language of Publication
- English
- Unique Identifier
- 73185091
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- MeSH Heading (Major)
- Blood Preservation|*; Sulfones|*
- MeSH Heading
- Animal; Cattle; Cryoprotective Agents; Dimethyl Sulfoxide;
Erythrocytes; Freezing; Hemolysis; Human
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0011-2240
- Country of Publication
- UNITED STATES
Record 5 from database: MEDLINE
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- Title
- Deformylation of 4,4'-diformamidodiphenyl sulfone (DFD) by
plasma of certain mammals.
- Author
- Gleason LN; Vogh BP
- Address
-
- Source
- Biochem Pharmacol, 1971 Sep, 20:9, 2409-16
- Abstract
- Abstract unavailable online.
- Language of Publication
- English
- Unique Identifier
- 74014895
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- MeSH Heading (Major)
- Antimalarials|*BL; Formates|*ME; Sulfones|*BL
- MeSH Heading
- Amines|ME; Aminobenzoic Acids|ME; Animal; Chromatography,
Thin Layer; Dealkylation; Diazonium Compounds|ME; Dimethyl
Sulfoxide; Erythrocytes|ME; Guinea Pigs; In Vitro; Kinetics;
Mice; Rabbits; Rats; Species Specificity; Sulfadiazine|ME;
Sulfanilamides|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2952
- Country of Publication
- UNITED STATES
Record 6 from database: MEDLINE
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- Title
- Desulfurization of dibenzothiophene by Corynebacterium sp.
strain SY1.
- Author
- Omori T; Monna L; Saiki Y; Kodama T
- Address
- Department of Agricultural Chemistry, Faculty of
Agriculture, University of Tokyo, Japan.
- Source
- Appl Environ Microbiol, 1992 Mar, 58:3, 911-5
- Abstract
- Strain SY1, identified as a Corynebacterium sp., was
isolated on the basis of the ability to utilize
dibenzothiophene (DBT) as a sole source of sulfur. Strain
SY1 could utilize a wide range of organic and inorganic
sulfur compounds, such as DBT sulfone, dimethyl sulfide,
dimethyl sulfoxide, dimethyl sulfone, CS2, FeS2, and even
elemental sulfur. Strain SY1 metabolized DBT to
dibenzothiophene-5-oxide, DBT sulfone, and
2-hydroxybiphenyl, which was subsequently nitrated to
produce at least two different hydroxynitrobiphenyls during
cultivation. These metabolites were separated by silica gel
column chromatography and identified by nuclear magnetic
resonance, UV, and mass spectral techniques. Resting cells
of SY1 desulfurized toluenesulfonic acid and released
sulfite anion. On the basis of these results, a new DBT
degradation pathway is proposed.
- Language of Publication
- English
- Unique Identifier
- 92246502
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- MeSH Heading (Major)
- Corynebacterium|GD/*ME; Sulfur|*ME; Thiophenes|*ME
- MeSH Heading
- Biodegradation; Chromatography; Kinetics; Sulfites|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0099-2240
- Country of Publication
- UNITED STATES
Record 7 from database: MEDLINE
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- Title
- Effects of dimethyl sulfone (DMSO2) on early gametogenesis
in Caenorhabditis elegans: ultrastructural aberrations and
loss of synaptonemal complexes from pachytene nuclei.
- Author
- Goldstein P; Magnano L; Rojo J
- Address
- Department of Biological Sciences, University of Texas, El
Paso 79968.
- Source
- Reprod Toxicol, 1992, 6:2, 149-59
- Abstract
- The free-living nematode Caenorhabditis elegans has been
used extensively for studies in developmental and
reproductive genetics. Recently, toxicologic studies have
been initiated using specific sex chromosome mutations. In
the present study, high incidence of male (him) mutants,
him-5 and him-8, were treated with dimethyl sulfone (DMSO2),
the primary metabolite of dimethyl sulfoxide (DMSO). In
addition to differential effects on X-chromosome
nondisjunction, loss of viability and fertility were
observed. Much lower concentrations of DMSO2 were required
to elicit the same aberrational effects characteristic of
DMSO (1); thus, the toxicity of the former was significantly
more potent. The observed decrease in life span was
associated with senescent morphology of meiotic prophase
nuclei, such that nuclei from young and old specimens could
not be differentiated. Aging in oocytes at pachytene is
characterized by nucleo-cytoplasmic aberrations, increased
density of the nucleoplasm and cytoplasm, and decrease in
numbers of mitochondria. Increasing concentrations of DMSO2
resulted in a corresponding decrease in fertility and
increased production of abnormal gametes. At DMSO2
concentrations higher than 1.0%, synaptonemal complexes (SC)
were absent from pachytene nuclei; thus, effective pairing
and segregation of homologous chromosomes was prohibited.
Since the SC is essential for regulating pairing and
subsequent separation of bivalents, the lack of an SC
explains the loss of fertility, due to the production of
unbalanced gametes, observed in DMSO2-treated specimens.
- Language of Publication
- English
- Unique Identifier
- 92273960
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- MeSH Heading (Major)
- Caenorhabditis|*DE/UL; Gametogenesis|*DE; Meiosis|*DE;
Mutagens|*; Sulfones|PK/*TO
- MeSH Heading
- Animal; Female; Male; Microscopy, Electron;
Mitochondria|UL; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0890-6238
- Country of Publication
- UNITED STATES
Record 8 from database: MEDLINE
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- Title
- Syntheses and biologic studies of steroidal methyl
sulfides and sulfones.
- Author
- Shafiullah; Dua PR; Srimal RC; Ansari SA
- Address
- Department of Chemistry, Aligarh Muslim University, India.
- Source
- Steroids, 1991 Nov, 56:11, 562-5
- Abstract
- Reactions of cholest-5-ene (I) and its 3 beta-chloro (II)
and 3 beta-acetoxy (III) analogs with
trimethylchlorosilane-dimethyl sulfoxide in dry acetonitrile
furnish cholest-4-en-6 beta-yl methyl sulfide (IV) and its 3
beta-chloro (V) and 3 beta-acetoxy (VI) analogs. Oxidation
of (IV) with m-chloroperbenzoic acid affords cholest-4-en-6
beta-yl methyl sulfone (VII) and 4 alpha, 5-epoxy-5
alpha-cholestan-6 beta-yl methyl sulfone (VIII). Under
similar reaction conditions, V furnishes 3
beta-chlorocholest-4-en-6 beta-yl methyl sulfone (IX), while
VI gives 3 beta-acetoxycholest-4-en-6 beta-yl methyl sulfone
(X) and 3 beta-acetoxy-4 alpha, 5-epoxy-5 alpha-cholestan-6
beta-yl methyl sulfone (XI). The structures of these
compounds were established on the basis of analytic and
spectral data. Some of these compounds have been evaluated
for their possible biologic activities.
- Language of Publication
- English
- Unique Identifier
- 92263386
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- MeSH Heading (Major)
- Autonomic Nervous System|*DE; Blood Pressure|*DE; Central
Nervous System|*DE; Steroids|*CS/PD; Sulfides|*CS/PD;
Sulfones|*CS/PD
- MeSH Heading
- Animal; Cats; Mice; Molecular Structure; Support, Non-U.S.
Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0039-128X
- Country of Publication
- UNITED STATES
Record 9 from database: MEDLINE
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- Title
- Effect of dimethyl sulfoxide on sulindac disposition in
rats.
- Author
- Swanson BN; Mojaverian P; Boppana VK; Dudash MR
- Address
-
- Source
- Drug Metab Dispos, 1981 Nov, 9:6, 499-502
- Abstract
- Sulindac and dimethyl sulfoxide (DMSO) are both effective
antiinflammatory agents in man. Since the sulfoxide moiety
in these compounds is metabolized similarly, a biochemical
interaction between the two drugs in vivo was thought to be
possible. After iv injections of sulindac (5 mg/kg), plasma
concentrations of sulindac, and its sulfide and sulfone
metabolites, were measured in normal rats and in rats that
had received, 30 min earlier, a single ip dose of DMSO (0.1,
0.5, or 1.0 ml). The half-life of sulindac (normally 94 min)
was increased significantly by DMSO (0.1, 0.5, or 1.0 ml).
The half-life of sulindac (normally 94 min) was increased
significantly by DMSO (408 min after 1.0 ml of DMSO). Plasma
sulfide metabolite levels were reduced in a dose-related
manner by DMSO (93% reduction in peak concentration after
1.0 ml of DMSO). Sulfone metabolite concentration was also
significantly diminished by the highest dose of DMSO.
Similarly, DMSO was shown to decrease conversion of sulindac
to sulfide and sulfone metabolites by rat liver enzymes in
vitro. Sulfoxide reductase was more sensitive to DMSO
inhibition than was sulfoxide oxidase both in vivo and in
vitro. These data demonstrate that DMSO can significantly
alter in vivo the formation of the pharmacologically active,
sulfide metabolite of sulindac; therefore, concurrent use of
DMSO and sulindac should be approached with caution.
- Language of Publication
- English
- Unique Identifier
- 82138346
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- MeSH Heading (Major)
- Dimethyl Sulfoxide|ME/*PD; Indenes|*ME; Liver|*ME;
Sulindac|AA/*ME
- MeSH Heading
- Animal; Dose-Response Relationship, Drug; Drug
Interactions; Half-Life; Kinetics; Male; Rats; Rats, Inbred
Strains; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0090-9556
- Country of Publication
- UNITED STATES
Record 10 from database: MEDLINE
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- Title
- Dimethyl sulfone: isolation from human urine.
- Author
- Williams KI; Burstein SH; Layne DS
- Address
-
- Source
- Arch Biochem Biophys, 1966 Jan, 113:1, 251-2
- Abstract
- Abstract unavailable online.
- Language of Publication
- English
- Unique Identifier
- 66160160
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- MeSH Heading (Major)
- Sulfones|*
- MeSH Heading
- Adult; Child; Child, Preschool; Chromatography, Gas;
Female; Human; In Vitro; Male; Urine
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-9861
- Country of Publication
- UNITED STATES
Record 11 from database: MEDLINE
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- Title
- Dimethyl sulfone: isolation from cows' milk.
- Author
- Williams KI; Burstein SH; Layne DS
- Address
-
- Source
- Proc Soc Exp Biol Med, 1966 Jul, 122:3, 865-6
- Abstract
- Abstract unavailable online.
- Language of Publication
- English
- Unique Identifier
- 67017073
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- MeSH Heading (Major)
- Milk|*AN; Sulfones|*AN
- MeSH Heading
- Animal; Cattle; Chemistry; Chromatography, Gas; In Vitro
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0037-9727
- Country of Publication
- UNITED STATES
Record 12 from database: MEDLINE
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- Title
- Sulfone metabolite of sulindac inhibits mammary
carcinogenesis.
- Author
- Thompson HJ; Jiang C; Lu J; Mehta RG; Piazza GA; Paranka
NS; Pamukcu R; Ahnen DJ
- Address
- AMC Cancer Research Center, Lakewood, Colorado 80214, USA.
- Source
- Cancer Res, 1997 Jan, 57:2, 267-71
- Abstract
- Sulindac sulfoxide, a commonly prescribed
anti-inflammatory drug, has cancer chemopreventive activity.
During its metabolism, the inactive prodrug sulindac
sulfoxide undergoes either reduction to the active
anti-inflammatory metabolite sulindac sulfide or
irreversible oxidation to sulindac sulfone, which lacks
prostaglandin synthetase inhibitory activity. Interestingly,
sulindac sulfone has been reported to have cancer
chemopreventive activity. The objective of the experiments
reported here was to investigate the chemopreventive
activity of sulindac sulfone against mammary carcinogenesis
and to study its mechanism. Rats were injected with either
12.5 or 37.5 mg of 1-methyl-1-nitrosourea (MNU)/kg body
weight at 50 days of age. Sulindac sulfone was incorporated
into a purified diet at a concentration of either 0.03 or
0.06% (w/w) and fed to rats beginning 7 days after the
injection of MNU. Sulindac sulfoxide at a level of 0.06%
(w/w) was fed as a reference for comparison. Thirty rats
were assigned to each dietary group treated with the high
dose of MNU, and 44 rats were assigned to each dietary group
treated with the low dose of MNU. The sulfone reduced cancer
incidence and the number of cancers per rat irrespective of
the dose of MNU injected, and its chemopreventive activity
was comparable to that of sulindac sulfoxide. Cancer latency
was also prolonged significantly by sulindac sulfone; the
effect was particularly notable at the low dose of
carcinogen, at which the prolongation of latency was >8
weeks. The sulfone inhibited the occurrence of mammary
carcinomas that were classified as having either a wild-type
or a mutant codon 12 in the Ha-ras gene; however, the
inhibitory effect was greater against carcinomas with a
mutant Ha-ras genotype. Using a mammary gland organ culture
transformation assay, it was observed that sulindac sulfone
also inhibited the formation of
7,12-dimethylbenz(a)anthracene-induced hyperplastic alveolar
nodules and that the inhibitory activity of the sulfone was
comparable to that of the sulfoxide. These data indicate
that the observed effect of the sulfone on mammary
carcinogenesis in vivo is likely to be due to a
tissue-specific effect rather than to other systemic
effects. The findings that both the prodrug and the sulfone
inhibited carcinogenesis in vivo and nodule formation in
organ culture and that the sulfone lacks inhibitory activity
on prostaglandin synthesis suggest a mechanism(s) of
chemoprevention that is independent of the prostaglandin
pathway. A candidate mechanism for the apparent clonal
selection pressure exerted by the sulfone against mammary
carcinogenesis is apoptosis. To test this hypothesis, MCF-7
cells were exposed to a range of concentrations of sulindac
sulfone and sulfoxide. Both compounds inhibited cell growth
and induced apoptosis in the absence of necrosis.
Collectively, these data support a specific chemopreventive
effect of sulindac sulfone against mammary carcinogenesis
and indicate that this compound may have a selective effect
against carcinogenesis involving alterations in the signal
transduction cascade of which Ha-ras is a component.
Evidence is consistent with the involvement of apoptosis in
the cancer-inhibitory activity observed.
- Language of Publication
- English
- Unique Identifier
- 97153276
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- MeSH Heading (Major)
- Antineoplastic Agents|*TU; Mammary Neoplasms,
Experimental|CI/GE/*PC; Sulindac|*AA/TU
- MeSH Heading
- Animal; Carcinogens|AD; Drug Screening Assays, Antitumor;
Female; Genes, ras; Methylnitrosourea|AD; Organ Culture;
Rats; Rats, Sprague-Dawley; Support, Non-U.S. Gov't;
Support, U.S. Gov't, Non-P.H.S.;
9,10-Dimethyl-1,2-benzanthracene
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-5472
- Country of Publication
- UNITED STATES
Record 13 from database: MEDLINE
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- Title
- Persistence of fensulfothion in a sandy-loam soil and
uptake by rutabagas, carrots and radishes using microplots.
- Author
- Greenhalgh R; Read DC
- Address
-
- Source
- J Environ Sci Health [B], 1981, 16:3, 363-79
- Abstract
- Field microplots were treated with 141 and 282 ppm
fensulfothion and 37.1 and 74.2 ppm fensulfothion sulfone.
These concentrations are equivalent to field treatment rates
of 8.48 and 16.96 kg AI/ha, fensulfothion, and 2.23 and 4.47
kg AI/ha, fensulfothion sulfone, respectively, for banded
application (10 cm wide, rows 80 cm apart). The half-lives
in a sandy loam soil were 30-39 and 14-23 days,
respectively. Fensulfothion sulfone and sulfide were the
main derivatives found in fensulfothion treated soil. The
maximum levels of these derivatives were 21.22 and 22.95 ppm,
respectively for the 8.48 kg/ha treatment and 33.90 and
42.45 ppm, respectively, for the higher treatment, which
occurred between 30-60 days. Carrots appeared to take up
more fensulfothion from soil than rutabagas or radishes. The
residue levels at harvest decreased in the order carrot peel
greater than pulp greater than rutabagas root greater than
peel greater than pulp. Residue levels of fensulfothion and
sulfone in radishes were similar to those found in
rutabagas. The ratio sulfoxide/sulfone in rutabagas ranged
from 0.4-1.5 and in carrots from 1.7-7.6. This phenomenon is
thought to be due to oxidative enzyme systems present in
rutabagas. Dimethyl phosphorothioic acid, but not dimethyl
phosphoric acid was detected (max. 1.33 ppm) in some
rutabagas samples but not in carrots.
- Language of Publication
- English
- Unique Identifier
- 81240591
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- MeSH Heading (Major)
- Insecticides, Organothiophosphate|*AN;
Organothiophosphorus Compounds|AA/*AN/ME; Soil
Pollutants|*AN; Vegetables|*AN
- MeSH Heading
- Brassica|ME; Dose-Response Relationship, Drug; Drug
Stability; Half-Life; Pesticide Residues|AN; Plants,
Edible|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0360-1234
- Country of Publication
- UNITED STATES
Record 14 from database: MEDLINE
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- Title
- Structure-activity relationships of retinoids in
developmental toxicology. IV. Planar Cisoid conformational
restriction.
- Author
- Willhite CC; Dawson MI
- Address
- Department of Health Services, State of California, Toxic
Substances Control Program, Berkeley 94710.
- Source
- Toxicol Appl Pharmacol, 1990 Apr, 103:2, 324-44
- Abstract
- To evaluate the influence of the three-dimensional
configuration of retinoids on teratogenic activity, 14
retinoids were studied in hamsters. Retinoids with a
conformational restriction of the retinoic acid polyene
chain adjacent to the beta-cyclogeranylidene ring showed
increased teratogenic potency and retinoids with aromatic
conformational restriction adjacent to the polar terminus
showed potency equivalent to retinoic acid. Conformational
restriction of the polyene chain that permits rotation of
the bond adjacent to the beta-cyclogeranylidene ring
abolished teratogenic activity. Incorporation of dimethyl
substituents at positions corresponding to C1 and C4
positions of retinoic acid enhanced teratogenic potency.
Elimination of the twist chair conformation of gem-dimethyl
substituents via incorporation of a benzothiopyran or
substituted planar aromatic ring decreased teratogenic
potency. Planar cisoid conformational restriction alone was
insufficient to confer teratogenic activity in that
elimination of the polar terminus abolished teratogenic
activity. That an acidic polar terminus, as contrasted to a
carboxyl residue per se, was required for teratogenic
activity was illustrated by administration of a retinoidal
phenyl sulfone which was metabolized to the corresponding
teratogenic sulfonic acid. Retinoid teratogenicity in
hamsters depends upon the assumption of a 10,11 cisoid
and/or 12,13 cisoid rotameric form by a conjugated spacer
greater than five carbon atoms in length located between a
hydrophobic ring system and an acidic terminus, ionized at
physiologic pH. Comparison of the relative teratogenic
potencies of this series of conformationally restricted
retinoids with their activities in assays for
chemoprevention activity showed that those analogs with high
intrinsic control of epithelial or mesenchymal cell
differentiation were also the more potent teratogens. The
results suggest that those biochemical mechanisms
responsible for retinoid control of normal adult or
neoplastic cell differentiation also mediate retinoid-induced
teratogenesis.
- Language of Publication
- English
- Unique Identifier
- 90232521
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- MeSH Heading (Major)
- Abnormalities, Drug-Induced|*; Fetal Development|*DE;
Fetal Diseases|*CI; Retinoids|*TO
- MeSH Heading
- Animal; Comparative Study; Dose-Response Relationship,
Drug; Female; Fetal Death; Fetal Resorption; Hamsters;
Molecular Conformation; Pregnancy; Structure-Activity
Relationship; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0041-008X
- Country of Publication
- UNITED STATES
Record 15 from database: MEDLINE
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- Title
- Unexpected similarity of the structures of the weakly
toxic amanitin (S)-sulfoxide and the highly toxic (R)-sulfoxide
and sulfone as revealed by proton nuclear magnetic resonance
and X-ray analysis.
- Author
- Wieland T; Götzendörfer C; Dabrowski J; Lipscomb WN;
Shoham G
- Address
-
- Source
- Biochemistry, 1983 Mar, 22:5, 1264-71
- Abstract
- The three-dimensional structures of the slightly toxic
diastereomeric (S)-sulfoxide of 6'-O-methyl-alpha-amanitin
[6'-O-Me-alpha-ama (S)-sulfoxide, 4] and of the
corresponding highly toxic sulfone 5 have been determined by
X-ray diffraction analysis. The same derivatives along with
6'-O-methyl-alpha-amanitin [O-Me-alpha-ama (R)-sulfoxide, 3]
and the corresponding thioether (O-Me-alpha-ama sulfide, 6]
have been investigated in dimethyl sulfoxide solutions by
360-MHz 1H NMR spectroscopy including nuclear Overhauser
effects (NOE). In addition alpha-amanitin (2) has been
reinvestigated by this high-resolution method involving the
identification of the ABMX systems of the tryptophan,
cysteine, and asparagine and discrimination between the
glycine residues. The structures of compounds 2-6 are
compared with the structure of beta-amanitin which was
solved previously by X-ray structure analysis. The results
are (1) the structures in the crystalline state of the (S)-sulfoxide
4 and sulfone 5 are practically identical and (2) in
dimethyl sulfoxide solution the structures of compounds 4
and 5 are likewise identical with each other and with those
of the (R)-sulfoxide 3 and the thioether 6. The general
structure of the peptide backbone of the alpha-amanitin
derivatives investigated here almost corresponds to that of
beta-amanitin (1), the main difference being a rotated plane
of the peptide bond between the asparagine and cysteine
residue. In order to explain the lack of high toxicity in
the (S)-sulfoxide 4 we tentatively suggest alternative
hydrogen bonding of a donor from the protein, or
displacement of the R oxygen to the S oxygen of a hydrogen
bond donor. This alternative bonding or displacement might
not occur in the sulfoxide 4. Other explanations which
include local conformational changes in the inhibitors or a
difference between the SO and SO2 local dipoles are also
possible.
- Language of Publication
- English
- Unique Identifier
- 83178939
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- MeSH Heading (Major)
- Amanitins|*/TO
- MeSH Heading
- Mathematics; Nuclear Magnetic Resonance; Stereoisomerism;
Support, U.S. Gov't, P.H.S.; X-Ray Diffraction
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2960
- Country of Publication
- UNITED STATES
Record 16 from database: MEDLINE
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- Title
- Cloning and characterization of genes encoding an enzyme
which oxidizes dimethyl sulfide in Acinetobacter sp. strain
20B.
- Author
- Horinouchi M; Kasuga K; Nojiri H; Yamane H; Omori T
- Address
- Biotechnology Research Center, University of Tokyo, Japan.
- Source
- FEMS Microbiol Lett, 1997 Oct, 155:1, 99-105
- Abstract
- Acinetobacter sp. strain 20B was isolated based on the
ability to utilize dimethyl sulfide as the sole sulfur
source. Since strain 20B oxidized indole as well as dimethyl
sulfide, indigo production by recombinant Escherichia coli
clones carrying Acinetobacter DNA was used as a selection
for cloning genes encoding dimethyl sulfide oxidation genes.
The gene encoding an indole-oxidizing enzyme was also found
to oxidize dimethyl sulfide. The dimethyl sulfide-oxidizing
enzyme genes consisted of six open reading flames designated
dsoABCDEF. The deduced amino acid sequences of dsoABCDEF
were homologous with those of the multicomponent phenol
hydroxylases. DsoABCDEF oxidized dimethyl sulfide to
dimethyl sulfoxide, and dimethyl sulfoxide to dimethyl
sulfone.
- Language of Publication
- English
- Unique Identifier
- 98005684
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- MeSH Heading (Major)
- Acinetobacter|*EN/*GE/ME; Genes, Bacterial|*; Sulfides|*ME
- MeSH Heading
- Cloning, Molecular; Comparative Study; Escherichia coli|GE;
Hydroxylases|GE/ME; Oxidation-Reduction; Oxygenases|GE/ME;
Restriction Mapping; Substrate Specificity
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0378-1097
- Country of Publication
- NETHERLANDS
Record 17 from database: MEDLINE
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- Title
- Biological effects of the metabolites of dimethyl
sulfoxide.
- Author
- Kocsis JJ; Harkaway S; Snyder R
- Address
-
- Source
- Ann N Y Acad Sci, 1975 Jan, 243:, 104-9
- Abstract
- In summary, the effects of dimethyl sulfoxide (DMSO) and
its metabolites, dimethyl sulfone (DMSO2) and dimethyl
sulfide (DMS), were studied in five selected systems in rats
and mice. DMSO enhanced the taurine excretion and the
lethality produced by such aromatic hydrocarbons as benzene
and chlorobenzene in rats. In mice, DMSO decreased the
toxicity such cholinesterase inhibitors as paraoxon and
octamethyl pyrophosphoramide. DMSO also lowered the body
temperture of rats and reduced the motor activity of mice.
Although DMSO2, the major metabolite of DMSO, was not
effective in increasing the lethality of solvent
hydrocarbons, it seemed to be quite as effective with
respect to the other effects. DMS, although quite potent
with respect to lowering body temperature and reducing motor
activity, was relatively ineffective otherwise. Thus each of
the metabolites has a spectrum of activity different from
the parent compound; DMSO has the widest spectrum and DMS
the narrowest. It remains to be determined whether the
therapeutic effects of DMSO are related to the experimental
effects reported above in animals, and whether DMSO2 and DMS
may share any of the therapeutic effects of DMSO.
- Language of Publication
- English
- Unique Identifier
- 75163079
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- MeSH Heading (Major)
- Dimethyl Sulfoxide|*AA/ME/PD; Sulfur Oxides|*PD
- MeSH Heading
- Animal; Benzene|TO; Body Temperature|DE; Cholinesterase
Inhibitors|TO; Depression, Chemical; Drug Synergism;
Hydrocarbons|TO; Hypnotics and Sedatives|PD; Lethal Dose 50;
Mice; Motor Activity|DE; Rats; Support, U.S. Gov't, Non-P.H.S.;
Taurine|ME/UR; Time Factors; Tranquilizing Agents|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0077-8923
- Country of Publication
- UNITED STATES
Record 18 from database: MEDLINE
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- Title
- A possible chemical explanation for the events associated
with the death of Gloria Ramirez at Riverside General
Hospital [see comments]
- Author
- Grant PM; Haas JS; Whipple RE; Andresen BD
- Address
- Forensic Science Centre, Lawrence Livermore National
Laboratory, Livermore, CA 94550, USA.
- Source
- Forensic Sci Int, 1997 Jun, 87:3, 219-37
- Abstract
- The events associated with the death of Gloria Ramirez at
Riverside General Hospital on 19 February 1994 have been
portrayed as a major medical mystery. A potential chemical
explanation for this incident has been developed. The
hypothetical scenario depends upon the oxidation of a common
solvent, dimethyl sulfoxide, through dimethyl sulfone to
dimethyl sulfate. The latter compound is a volatile and
highly toxic agent that can be quite hazardous to humans in
small amounts. It is also environmentally nonpersistent.
Much of the mystery surrounding the circumstances at the
hospital may be explainable if this postulated metabolic
pathway took place at the time of the emergency room
incident. Although dimethyl sulfate was not detected in any
analyses pertinent to this event, there are plausible
scientific explanations to account for that fact. The
sulfate anion, a hydrolysis product of dimethyl sulfate, was
measured at an appreciably elevated concentration in
Ramirez' blood. The descriptions of the symptoms of the
hospital-staff victims appear quite consistent with dimethyl
sulfate exposures. This paper attempts to make some sense of
the reported data and eyewitness accounts, and perhaps
provide new insight for any future research that could
further explain this reported occurrence of toxic exposure.
- Language of Publication
- English
- Unique Identifier
- 97391234
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- MeSH Heading (Major)
- Cause of Death|*; Dimethyl Sulfoxide|*ME; Forensic
Medicine|*MT; Mutagens|ME/*PO; Sulfones|*ME; Sulfuric Acid
Esters|ME/*PO
- MeSH Heading
- Blood Chemical Analysis; California; Emergency Service,
Hospital; Human; Oxidation-Reduction
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0379-0738
- Country of Publication
- IRELAND
Record 19 from database: MEDLINE
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- Title
- Identification of biotin sulfone, bisnorbiotin methyl
ketone, and tetranorbiotin-l-sulfoxide in human urine.
- Author
- Zempleni J; McCormick DB; Mock DM
- Address
- Department of Pediatrics, University of Arkansas for
Medical Sciences, Little Rock, USA.
- Source
- Am J Clin Nutr, 1997 Feb, 65:2, 508-11
- Abstract
- In previous studies using the HPLC and avidin-binding
assay, five unidentified avidin-binding substances were
observed in human urine. The present study investigated the
identity of these substances. Urine was collected before and
after intravenous administration of 18.5 mumol biotin to
healthy adults. Unknown substances 1 and 3 were initially
identified as biotin sulfone and bisnorbiotin methyl ketone,
respectively, by coelution with authentic standards on HPLC.
Identities were confirmed by thin-layer chromatography and
by derivatization with p-dimethyl-aminocinnamaldehyde. As
expected for biotin metabolites, the urinary excretion of
biotin sulfone and bisnorbiotin methyl ketone increased with
biotin administration. The urinary excretion of biotin
sulfone increased 21-fold from 0.2 nmol/h before to 4.2 nmol/h
after administration; the excretion of bisnorbiotin methyl
ketone increased 130-fold from 0.4 to 51.8 nmol/h. At
presumed steady state in free-living subjects (n = 6),
biotin sulfone and bisnorbiotin methyl ketone accounted for
3.6% and 7.9% of total biotin excretion, respectively.
Traces of tetranorbiotin-l-sulfoxide were also identified by
using thin-layer chromatography and derivatization with p-dimethylaminocinnamaldehyde.
However, tetranorbiotin-l-sulfoxide was not detectable in
urine by the HPLC and avidin-binding assay because this
metabolite has weak avidin-binding affinity. We conclude
that biotin sulfone and bisnorbiotin methyl ketone are
present in measurable quantities in human urine; their
quantitation should allow more accurate studies on human
biotin metabolism and turnover.
- Language of Publication
- English
- Unique Identifier
- 97174877
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- MeSH Heading (Major)
- Biotin|*AA/AD/*ME/UR; Sulfones|*UR; Sulfoxides|*UR
- MeSH Heading
- Adult; Chromatography, High Pressure Liquid|MT;
Chromatography, Thin Layer|MT; Female; Human; Injections,
Intravenous; Male; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0002-9165
- Country of Publication
- UNITED STATES
Record 20 from database: MEDLINE
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- Title
- Permeation of lipophilic drugs through synthetic
elastomers.
- Author
- Bruck SD; Kojima M; Kadoma Y; Masuhara E
- Address
-
- Source
- Med Prog Technol, 1983, 10:3, 161-9
- Abstract
- Permeability studies were carried out with three
lipophilic drugs, namely, phenytoin and primidone (both
widely used in the treatment of epilepsies and convulsive
disorders), and dapsone (a sulfone antimicrobial agent used
in the treatment of leprosy and to a lesser extent in
dermatitis herpetiformis) through silica-filled
poly(dimethyl siloxane) (Silastic) membranes, and
anisotropic membranes of poly(ether-urethane)/poly(dimethyl
siloxane) block copolymer (Avcothane, Cardiothane). These
polymers are used in medical implants and in various
cardiovascular devices. While both polymers were permeable
to the drugs, the transport properties differed
significantly. In the case of the poly(dimethyl siloxane)
there was an initial large burst effect, followed by an
exponential decrease in the rate of drugs released through
the polymer films, although with dapsone the release rate
became essentially constant between 100-180 h at 37 degrees
C. In the case of the anisotropic films of the poly(ether-urethane)/poly(dimethyl
siloxane) block copolymer, the permeabilities were much
higher. Significantly, phenytoin exhibited essentially
constant rate (zero-order) kinetics between 25-150 h,
showing only a moderate burst effect that is probably not
significant therapeutically. Importantly, dapsone showed
neither a burst effect nor any significant time lag, and the
release followed constant rate (zero-order) kinetics between
12-80 h, followed by only a moderate decrease in drug
concentration up to 140 h (the experimental end-point). The
diffusion coefficients calculated from initial desorption
data at 37 degrees C for the poly(ether-urethane)/poly(dimethyl
siloxane) block copolymer are as follows: phenytoin = 8.6 X
10(-9) cm2/s, primidone = 2.8 X 10(-9) cm2/s, and dapsone =
2.4 X 10(-8) cm2/s.(ABSTRACT TRUNCATED AT 250 WORDS)
- Language of Publication
- English
- Unique Identifier
- 85110700
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- MeSH Heading (Major)
- Dapsone|*ME; Membranes, Artificial|*; Phenytoin|*ME;
Polymers|*; Primidone|*ME; Silicone Elastomers|*
- MeSH Heading
- Kinetics; Microscopy, Electron, Scanning; Permeability;
Polyurethanes; Support, Non-U.S. Gov't; Time Factors
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0047-6552
- Country of Publication
- GERMANY, WEST
Record 21 from database: MEDLINE
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- Title
- DMSO is a substrate for chloroperoxidase.
- Author
- Geigert J; DeWitt SK; Neidleman SL; Lee G; Dalietos DJ;
Moreland M
- Address
-
- Source
- Biochem Biophys Res Commun, 1983 Oct, 116:1, 82-5
- Abstract
- Dimethyl sulfoxide has been used as a nonaqueous organic
solvent in haloperoxidase reactions. However, it has been
found that this solvent is not inert under chloroperoxidase
reaction conditions, forming the halosulfoxide, the sulfone,
and the halosulfone. The biological significance of this
finding is briefly discussed.
- Language of Publication
- English
- Unique Identifier
- 84052565
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- MeSH Heading (Major)
- Chloride Peroxidase|*ME; Dimethyl Sulfoxide|*ME;
Peroxidases|*ME
- MeSH Heading
- Fungi|EN; Oxidation-Reduction
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-291X
- Country of Publication
- UNITED STATES
Record 22 from database: MEDLINE
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- Title
- Induction of NAD(P)H:quinone reductase in human peripheral
blood lymphocytes.
- Author
- Gordon GB; Prochaska HJ; Yang LY
- Address
- Department of Pharmacology and Molecular Sciences, Johns
Hopkins University School of Medicine, Baltimore, MD 21205.
- Source
- Carcinogenesis, 1991 Dec, 12:12, 2393-6
- Abstract
- The induction of quinone reductase [QR; NAD(P)H:(quinone
acceptor) oxidoreductase; EC 1.6.99.2] in cultured cells and
animal tissues of rodents has provided useful information on
mechanisms of protection against carcinogens. We have
developed a simple and efficient microtiter plate assay for
the direct measurement of QR basal activity and inducibility
in human peripheral blood lymphocytes (unstimulated, mitogen-stimulated
and Epstein-Barr virus-transformed) grown in suspension
culture. In these cells, QR was induced by monofunctional (electrophilic)
inducers (i.e. 1,2-dithiole-3-thione, dimethyl fumarate,
methyl vinyl sulfone) but not by bifunctional inducers (i.e.
1,1'-azonaphthalene, beta-naphthoflavone,
2,3,7,8-tetrachlorodibenzo-p-dioxin). QR is a major enzyme
of xenobiotic metabolism that carries out obligatory
two-electron reductions and thereby protects cells against
the toxicity of quinones. It is induced in many tissues
coordinately with other enzymes that protect against
electrophiles. Since lymphocytes can be sampled easily and
repetitively in man, this system may provide a simple
short-term marker for assessing the capacity of tissues to
detoxify electrophiles, such as quinones, and for measuring
the response to inducers.
- Language of Publication
- English
- Unique Identifier
- 92083635
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- MeSH Heading (Major)
- Lymphocytes|DE/*EN; NAD(P)H Dehydrogenase (Quinone)|*BI/BL
- MeSH Heading
- Adult; Aged; Cell Transformation, Viral|PH; Cells,
Cultured; Enzyme Induction; Female; Fumarates|PD;
Herpesvirus 4, Human|PH; Human; Lymphocyte Transformation|PH;
Male; Middle Age; Mitogens|PD; Sulfones|PD; Support, Non-U.S.
Gov't; Support, U.S. Gov't, P.H.S.; Thiones|PD;
Thiophenes|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0143-3334
- Country of Publication
- UNITED STATES
Record 23 from database: MEDLINE
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- Title
- Effect of cross-linking agents on insulin associated
responses in adipocytes.
- Author
- Goren HJ; Kahn CR
- Address
-
- Source
- Can J Biochem, 1982, 60:10, 987-1000
- Abstract
- The effect of 10 bifunctional cross-linking agents and
four monofunctional analogues was studied on isolated
adipocytes. [125I]Insulin binding and degradation, basal and
insulin-stimulated glucose oxidation, and 3-O-methyl glucose
uptake were measured. Two cross-linkers, which possess
succinimide ester residues (disuccinimidyl suberate and
dithiobis(succinimidyl propionate)) and react selectively
with amino groups, appeared to react relatively specifically
with the insulin receptor. Both produced a slight
stimulation of basal glucose transport and metabolism, a
marked inhibition of insulin-stimulated glucose transport
and metabolism, and a marked decrease in insulin binding.
Pretreatment of cells with unlabelled insulin partially
blocked the effect of disuccinimidyl suberate, and as has
been previously shown, disuccinimidyl suberate cross-linked
insulin to its receptor. A monofunctional analogue of these
compounds was 100-fold less active in altering cellular
metabolic activity. Bisimidates, such as dimethyl
suberimidate, dimethyl adipimidate, and dimethyl
dithiobispropionimidate, also react with free amino groups
but are more hydrophilic. These agents produced similar
effects on glucose oxidation as the succinimide esters, but
had little or no effect on insulin binding. The effects of
these agents are not blocked by insulin and they do not
cross-link insulin to its receptor. Mixed bifunctional
reagents containing either a succinimide ester or an imidate
and a group which reacts with thiols produced effects
similar to the cross-linkers containing two succinimide
groups or bisimidates, respectively. The bifunctional
arylating agents difluorodinitrobenzene and
bis(fluoronitrophenyl)sulfone produce marked effects on
insulin binding and glucose oxidation at micromolar
concentrations, but the monofunctional analogue
fluorodinitrobenzene is almost equally active suggesting
that with these compounds chemical modifications and not
cross-linking was important. With neither the mixed
bifunctional reagents, nor the arylating agents, did insulin
pretreatment alter the effect of cross-linker and none of
these agents cross-linked [125I]insulin to its receptor.
These data suggest that the insulin receptor possesses a
free amino group in a hydrophobic environment in its active
site. A reactive amino group in a hydrophilic environment as
well as other reactive groups are also present in some
component of the insulin receptor-effector complex. Chemical
modification or cross-linking of these functional groups
results in an inhibition or mimicking of insulin action.
Further study will be required to identify the exact locus
of these sites.
- Language of Publication
- English
- Unique Identifier
- 83076688
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- MeSH Heading (Major)
- Adipose Tissue|*ME; Cross-Linking Reagents|*PD;
Insulin|*ME; Receptors, Insulin|*ME
- MeSH Heading
- Animal; Cells, Cultured; Glucose|ME; Male; Rats; Rats,
Inbred Strains; Succinimides|PD; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-4018
- Country of Publication
- CANADA
Record 24 from database: MEDLINE
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- Title
- Growth inhibitory effects of dimethyl sulfoxide and
dimethyl sulfone on vascular smooth muscle and endothelial
cells in vitro.
- Author
- Layman DL
- Address
-
- Source
- In Vitro Cell Dev Biol, 1987 Jun, 23:6, 422-8
- Abstract
- The growth of bovine aortic smooth muscle and endothelial
cells was studied after exposure to dimethyl sulfoxide
(DMSO) or its major metabolite, dimethyl sulfone (DMSO2).
Both compounds caused a dose-dependent inhibition of cell
growth as determined by [3H]thymidine incorporation and by
counting the number of cells with time of exposure in
culture. The IC50 of DMSO (concentration which produces 50%
inhibition of growth) was 1% for smooth muscle cells and
2.9% for endothelial cells. Similarly, the IC50 of DMSO2 was
also 1% for smooth muscle cells, but was 1.8% for
endothelial cells. After a 4-d exposure to either compound,
the growth inhibition of smooth muscle cells was completely
reversible at 1%, partially reversible at 2 to 3% and
completely irreversible at 4%. By comparison, inhibition of
endothelial cell growth was completely reversible up to 4%
of either compound. It is concluded that the growth of
smooth muscle cells was similarly inhibited by DMSO and
DMSO2, but that smooth muscle cells were more susceptible
than endothelial cells to the growth inhibitory effects of
these compounds. In addition, DMSO2 was a more potent
inhibitor of cell growth than DMSO and its growth inhibition
was less reversible than that produced by DMSO.
- Language of Publication
- English
- Unique Identifier
- 87250195
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- MeSH Heading (Major)
- Dimethyl Sulfoxide|*PD; Endothelium|*CY/DE; Muscle,
Smooth, Vascular|*CY/DE; Sulfones|*PD
- MeSH Heading
- Animal; Aorta; Cattle; Cell Division|DE; Cell Survival|DE;
Cells, Cultured; Time Factors
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0883-8364
- Country of Publication
- UNITED STATES
Record 25 from database: MEDLINE
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- Title
- Cryoprotection by dimethyl sulfoxide and dimethyl sulfone.
- Author
- McGann LE; Walterson ML
- Address
-
- Source
- Cryobiology, 1987 Feb, 24:1, 11-6
- Abstract
- Preservation of cells and tissues at low temperatures
requires the presence of effective cryoprotectants with low
toxicity to which cells are relatively permeable. Two
similar compounds, dimethyl sulfoxide (DMSO) and dimethyl
sulfone (DMSO2), exhibit both features for cryoprotectants,
yet DMSO is a very effective cryoprotectant while DMSO2 is
ineffective. This anomaly was investigated by relating
observations on the phase behavior of DMSO and DMSO2 in
aqueous solutions to the recovery of human lymphocytes
frozen in the presence of these compounds. The lack of
cryoprotection in the presence of DMSO2 appears to be due to
the precipitation of DMSO2 from the solution at subzero
temperatures. The observation of reduced cell recovery after
freezing with increasing concentrations of DMSO2 implies
that cell damage is related to the amount of solid DMSO2
present. Precipitation of DMSO2 occurs both intra- and
extracellularly, but it is argued that intracellular
precipitation of DMSO2 is the damaging phenomenon.
Cryoprotective compounds are normally selected based on the
criteria of low toxicity and permeability to the plasma
membrane. An additional condition, solubility, must be
included for interpretation of experimental data and for
development of effective protocols for cryopreservation.
- Language of Publication
- English
- Unique Identifier
- 87132479
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- MeSH Heading (Major)
- Dimethyl Sulfoxide|*; Lymphocytes|*CY; Sulfones|*; Tissue
Preservation|*MT
- MeSH Heading
- Cell Survival; Freezing; Human; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0011-2240
- Country of Publication
- UNITED STATES
Record 26 from database: MEDLINE
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- Title
- Subunit associations of (Na+ + K+)-dependent adenosine
triphosphatase. Chemical cross-linking studies.
- Author
- Periyasamy SM; Huang WH; Askari A
- Address
-
- Source
- J Biol Chem, 1983 Aug, 258:16, 9878-85
- Abstract
- Cross-linking reactions of the alpha- and beta-subunits of
the purified membrane-bound enzyme with several reagents
were studied. In the presence of
1,5-difluoro-2,4-dinitrobenzene, formation of a cross-linked
alpha, beta-dimer was affected specifically by K+ + ATP or
enzyme phosphorylation. The same conditions affected the
formation of cross-linked alpha, alpha-dimer in the presence
of 4,4'-difluoro-3,3'-dinitrodiphenyl sulfone or
o-phenanthroline-Cu2+. Since noncovalent alpha,
beta-association has been established, the data suggest K+ +
ATP-induced or phosphorylation-induced changes in alpha,
beta-domain and alpha, alpha-domain of an oligomer of alpha,
beta-dimer. When the formation of cross-linked alpha, beta-dimer
or alpha, alpha-dimer was induced by phosphorylation, only
half of the subunits were cross-linked, suggesting the
existence of a cooperative tetramer of alpha, beta-dimer.
When microsomes or red cell membranes were exposed to 32Pi
under phosphorylation-induced cross-linking conditions, the
only products were alpha, beta-dimer and alpha, alpha-dimer,
indicating the existence of an oligomer of alpha, beta-dimer
in crude membranes. Subunits of the enzyme solubilized with
octaethylene glycol dodecyl ether, by methods that have been
suggested to yield unassociated alpha, beta-dimers,
underwent spontaneous cross-linking that was not affected by
enzyme dilution. Since the largest product was alpha 2 beta
2, the solubilized enzyme is at least a dimer of alpha,
beta-dimer. The findings establish that the membrane-bound
enzyme is an oligomer of alpha, beta-dimer. Whether or not a
single alpha, beta-dimer is capable of catalytic and
transport functions has not been determined.
- Language of Publication
- English
- Unique Identifier
- 83290912
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- MeSH Heading (Major)
- Cross-Linking Reagents|*; Na(+)-K(+)-Exchanging ATPase|*ME
- MeSH Heading
- Animal; Dimethyl Suberimidate; Dinitrofluorobenzene|AA;
Dogs; Glutaral; Kidney|EN; Macromolecular Systems;
Maleimides; Support, U.S. Gov't, P.H.S.; SITS|AA;
Thiocyanates
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 27 from database: MEDLINE
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- Title
- Folate antagonists. 19. Synthesis and antimalarial effects
of 6-(arylthio)-2,4-pteridinediamines.
- Author
- Elslager EF; Johnson JL; Werbel LM
- Address
-
- Source
- J Med Chem, 1981 Aug, 24:8, 1001-3
- Abstract
- A series of 6-(arylthio)-2,4-pteridinediamines (IIIa) was
prepared by allowing 6-chloro-2,4-pteridinediamine to react
with the requisite benzenethiols in dimethyl sulfone at
190-200 degrees C. Attempts at oxidation to the
corresponding sulfoxide (IIIb) or sulfone (IIIc) were
unsuccessful. The compounds exhibited a spectrum of
antibacterial activity similar to, but below the potency of,
the related quinazolinediamines and pteridinediamines.
Unlike these related types, however, they were devoid of
antimalarial activity when tested against a normal
drug-sensitive strain of Plasmodium berghei in mice by the
parenteral route.
- Language of Publication
- English
- Unique Identifier
- 82122391
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- MeSH Heading (Major)
- Antimalarials|*; Folic Acid Antagonists|*PD; Pteridines|CS/*PD
- MeSH Heading
- Animal; Bacteria|DE; Drug Screening; Mice
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2623
- Country of Publication
- UNITED STATES
Record 28 from database: MEDLINE
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- Title
- Apoptosis primarily accounts for the growth-inhibitory
properties of sulindac metabolites and involves a mechanism
that is independent of cyclooxygenase inhibition, cell cycle
arrest, and p53 induction.
- Author
- Piazza GA; Rahm AK; Finn TS; Fryer BH; Li H; Stoumen AL;
Pamukcu R; Ahnen DJ
- Address
- Cell Pathways, Inc., Denver, Colorado 80012-4526, USA.
- Source
- Cancer Res, 1997 Jun, 57:12, 2452-9
- Abstract
- Sulindac causes regression of and prevents recurrence of
colonic adenomas in patients with familial adenomatous
polyposis. Although cell cycle arrest and apoptosis have
been proposed, the mechanism of action is poorly understood.
In this study, we characterized the growth-inhibitory
effects of active metabolites of sulindac in cultured colon
adenocarcinoma cells by determining the contribution of
apoptosis and cell cycle arrest and the requirement for
cyclooxygenase (COX) inhibition and p53 involvement and
compared the effects of sulindac metabolites with the
chemotherapeutic drug, 5-fluorouracil (5-FU). Time course
and dose-response experiments demonstrated that increased
apoptosis paralleled the growth-inhibitory effects of the
sulfide and sulfone. A relationship among a series of
nonsteroidal anti-inflammatory drugs was observed between
potency for growth inhibition and ability to induce
apoptosis but not potency to inhibit COX. For example, the
sulfone was at least 5000-fold less potent than the sulfide
for inhibiting COX but only 6.5-fold less potent for
inducing apoptosis. Moreover, the prostaglandin analogue,
dimethyl-prostaglandin E2, failed to reverse the
apoptosis-inducing effects of the sulfide. Sulindac
metabolites caused G1 cell cycle arrest in proliferating
cells but were comparably effective in nonproliferating
cells. In contrast, 5-FU treatment was less effective in
nonproliferating cells. Combined treatment with sulindac
metabolites and 5-FU did not result in an additive apoptotic
response. Treatment of cells with 5-FU increased p53 protein
levels, whereas sulindac metabolites did not induce
expression. Saos-2 cells, which lack p53, responded to
sulindac metabolites but not 5-FU. These results show that
apoptosis primarily contributes to growth inhibition by
sulindac metabolites. The biochemical pathway does not
require COX inhibition or p53 induction and appears to be
fundamentally different from the apoptotic response to 5-FU.
- Language of Publication
- English
- Unique Identifier
- 97336030
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- MeSH Heading (Major)
- Apoptosis|*/DE; Cyclooxygenase Inhibitors|*ME/*PD; Protein
p53|*ME; Sulindac|*ME/*PD
- MeSH Heading
- Adenocarcinoma|ME/PA; Anti-Inflammatory Agents, Non-Steroidal|PD;
Cell Cycle|PH; Cell Division|DE; Cell Survival|DE; Colonic
Neoplasms|ME/PA; Dose-Response Relationship, Drug;
Fluorouracil|PD; Growth Inhibitors|PD; Human; Prostaglandin-Endoperoxide
Synthase|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't,
Non-P.H.S.; Time Factors; Tumor Cells, Cultured;
16,16-Dimethylprostaglandin E2|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0008-5472
- Country of Publication
- UNITED STATES
Record 29 from database: MEDLINE
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- Title
- Synthesis and elastase inhibitory activity of 6
alpha-chloro-2,2-dimethyl-3 alpha-(pivaloyloxy)methylpenam
sulfone, 6 alpha-chloro-2,2-dimethyl-3-exo-methylenepenam
sulfone, benzyl and methyl 6 alpha-substituted penicillanate
sulfones.
- Author
- Boschetti CE; Mascaretti OA; Cricco JA; Roveri OA
- Address
- Instituto de QuÆimica OrgÆanica de SÆintesis (CONICET-UNR),
Rosario, Argentina.
- Source
- Bioorg Med Chem, 1995 Jan, 3:1, 95-100
- Abstract
- The triflates and pivalates of 3
alpha-hydroxymethyl-6-substituted-2,2-dimethylpenam sulfones
3, 5; methyl and benzyl 6-substituted penicillanates 6-9 and
3-exo-methylene-6-substituted-2,2-dimethylpenam sulfone 4
were synthesized. These novel compounds were evaluated as
elastase inhibitors using porcine pancreatic elastase. The
effects that structural modifications of substituents on C-3
and C-6 in the penam nucleus have on elastase activity were
examined and several similarities and distinctions were
identified when compared to the reported penicillin esters
and amides elastase inhibitors.
- Language of Publication
- English
- Unique Identifier
- 96214701
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- MeSH Heading (Major)
- Pancreatopeptidase|*AI; Sulbactam|*AA/CS/PD; Sulfones|*CS/PD
- MeSH Heading
- Animal; Molecular Structure; Structure-Activity
Relationship; Support, Non-U.S. Gov't; Swine
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0968-0896
- Country of Publication
- ENGLAND
Record 30 from database: MEDLINE
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- Title
- Effects of dimethyl sulfoxide on the oxidative function of
human neutrophils.
- Author
- Beilke MA; Collins Lech C; Sohnle PG
- Address
-
- Source
- J Lab Clin Med, 1987 Jul, 110:1, 91-6
- Abstract
- Dimethyl sulfoxide (DMSO) has been demonstrated to
suppress the in vitro microbicidal activity of neutrophils.
In addition, this compound has been described as having
significant anti-inflammatory activity. These properties
have generally been attributed to the effectiveness of this
compound as a hydroxyl radical scavenger. However, DMSO can
also act as a reductant under certain conditions, yielding
its fully oxidized form, dimethyl sulfone (DMSO2), as the
product. Therefore, we evaluated the ability of these two
compounds to interfere with the production of oxidants other
than the hydroxyl radical by stimulated human neutrophils.
In a cell-free assay, DMSO was found to quench the oxidant
activity of hypochlorous acid. Neither DMSO nor DMSO2
reacted with superoxide, hydrogen peroxide, taurine
chloramine, or monochloramine in this system. However, both
DMSO and DMSO2 significantly suppressed the production of
superoxide, hydrogen peroxide, and hypochlorous acid by
human neutrophils stimulated with either phorbol myristate
acetate or opsonized zymosan. Neutrophil viability was not
reduced by either DMSO or DMSO2. Inhibition of the oxidative
function of stimulated neutrophils by DMSO may provide an
alternative explanation for the effects of this compound on
the microbicidal activity of neutrophils and as an in vivo
anti-inflammatory agent.
- Language of Publication
- English
- Unique Identifier
- 87252692
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- MeSH Heading (Major)
- Dimethyl Sulfoxide|*PD; Neutrophils|DE/*PH
- MeSH Heading
- Cell Survival|DE; Human; Support, U.S. Gov't, Non-P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2143
- Country of Publication
- UNITED STATES
Record 31 from database: MEDLINE
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- Title
- The absorption, metabolism and excretion of dimethyl
sulfoxide by rhesus monkeys.
- Author
- Layman DL; Jacob SW
- Address
-
- Source
- Life Sci, 1985 Dec, 37:25, 2431-7
- Abstract
- The absorption and excretion of dimethyl sulfoxide (DMSO)
were studied in Rhesus monkeys (Macaca mulatta) given daily
oral doses of 3 gms DMSO/kg B.W. for 14 days. DMSO and its
major metabolite, dimethyl sulfone (DMSO2), were measured in
serum, urine and feces by gas-liquid chromatography. DMSO
was absorbed rapidly, reached a steady state blood level
after 1 day and then was cleared from blood within 72 hrs
after ending treatment. Serum DMSO declined in a linear
fashion on semilogarithmic coordinates as described by
second order kinetics. It had a half-life of 16 hrs. DMSO2
appeared in blood within 2 hrs and reached a steady state
concentration after 4 days of treatment. DMSO2 was cleared
from blood about 120 hrs after DMSO administration was
stopped. Its half-life in blood was calculated to be 38 hrs.
Urinary excretion of unmetabolized DMSO and DMSO2 accounted
for about 60% and 16%, respectively, of the total ingested
dose. Neither DMSO nor DMSO2 was detected in fecal samples.
However, when added to fecal samples, DMSO was degraded
rapidly. Although dimethyl sulfide (DMS) was not measured,
some DMSO was metabolized to this compound because of the
particular sweetness of breath of the monkeys. We conclude
that the absorption of DMSO by monkeys is similar to that
for humans, but that its conversion to DMSO2 and urinary
elimination are more rapid in monkeys.
- Language of Publication
- English
- Unique Identifier
- 86091268
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- MeSH Heading (Major)
- Dimethyl Sulfoxide|BL/*ME/UR
- MeSH Heading
- Absorption; Animal; Chromatography, Gas; Feces|AN;
Half-Life; Kinetics; Macaca mulatta; Sulfones|BL/UR;
Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0024-3205
- Country of Publication
- ENGLAND
Record 32 from database: MEDLINE
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- Title
- Effects of oral dimethyl sulfoxide and dimethyl sulfone on
murine autoimmune lymphoproliferative disease.
- Author
- Morton JI; Siegel BV
- Address
-
- Source
- Proc Soc Exp Biol Med, 1986 Nov, 183:2, 227-30
- Abstract
- The results from several studies examining the effects of
DMSO on autoimmune phenomena have been inconclusive,
possibly because of differences in experimental models,
treatment regimens and doses employed. In the present
investigation, autoimmune strain MRL/lpr, C3H/lpr, and male
BXSB mice were placed on a continuous treatment regimen with
3% DMSO or 3% DMSO2 in the drinking water, ad libitum,
commencing at 1 to 2 months of age, before spontaneous
disease development could be detected. This represented
doses of 8-10 g/kg/day of DMSO and 6-8 g/kg/day of DMSO2.
Both compounds were observed to extend the mean life span of
MRL/lpr mice from 5 1/2 months to over 10 months of age. All
strains showed decreased antinuclear antibody responses and
significant diminution of lymphadenopathy, splenomegaly, and
anemia development. Serum IgG levels and spleen IgM antibody
plaque formation, however, did not differ from control
values. There was no indication of involvement of systemic
immunosuppressive or antiproliferative effects, and treated
animals were observed to remain healthy and vigorous with no
signs of toxicity. These results demonstrate that high doses
of both DMSO and its major in vivo metabolite, DMSO2,
provide significant protection against the development of
murine autoimmune lymphoproliferative disease. Possible
mechanisms of protection are discussed.
- Language of Publication
- English
- Unique Identifier
- 87017093
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- MeSH Heading (Major)
- Autoimmune Diseases|*DT; Dimethyl Sulfoxide|*TU;
Lymphoproliferative Disorders|*DT; Sulfones|*TU
- MeSH Heading
- Animal; Antibodies, Antinuclear|AN; Disease Models,
Animal; IgG|AN; IgM|AN; Male; Mice; Mice, Inbred C3H; Mice,
Mutant Strains; Spleen|AN; Support, Non-U.S. Gov't
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0037-9727
- Country of Publication
- UNITED STATES
Record 33 from database: MEDLINE
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- Title
- X-ray crystal structure of a dimethylene sulfone-bridged
ribonucleotide dimer in a single-stranded state.
- Author
- Hyrup B; Richert C; Schulte Herbrüggen T; Benner SA; Egli
M
- Address
- Department of Chemistry, Swiss Federal Institute of
Technology, ZÂurich.
- Source
- Nucleic Acids Res, 1995 Jul, 23:13, 2427-33
- Abstract
- A crystal structure has been solved for an analog of the
r(ApU) ribodinucleotide, r(Aso2U), where a bridging
non-ionic dimethylene sulfone linker replaces the
phosphodiester linking group found in natural RNA. Crystals
of the single-stranded state of r(Aso2U) were obtained from
water at 50 degrees C. In these crystals, one hydrogen bond
is formed between bases from different strands and base
stacking occurs in intermolecular 'homo-A' and 'homo-U'
stacks. Similar to typical oligoribonucleotides, the ribose
rings adopt N-type conformations and dihedral angles chi are
in the anti range. The all-trans rotamer of the
CH2-SO2-CH2-CH2 bridge was found, which leads to a large
adenine-uracil distance. Qualitative analysis of a NOESY
spectrum of the Aso2U part in r(Uso2Cso2Aso2U) dissolved in
a dimethylsulfoxide-D2O mixture indicates that the
conformation observed in the crystal is also populated in
solution. Comparison with the structure of r(Gso2C), which
has been crystallized in the Watson-Crick paired state,
shows that a rotation around zeta by +112 degrees leads from
the observed, single-stranded state to a conformation that
is compatible with formation of a duplex. A concerted
trans/gauche flip of alpha and gamma then yields the
standard conformer of A-type RNA helices. From the observed
structure of r(Gso2C) and other oligonucleotides it is
anticipated that this flip will also revert the ribose
pucker from C2'-exo to C3'-endo.
- Language of Publication
- English
- Unique Identifier
- 95357150
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- MeSH Heading (Major)
- RNA|*CH; Sulfones|*CH
- MeSH Heading
- Adenine|CH; Crystallization; Crystallography, X-Ray;
Dimethyl Sulfoxide; Hydrogen Bonding; Macromolecular
Systems; Molecular Structure; Nuclear Magnetic Resonance;
Nucleic Acid Conformation; Oligoribonucleotides|CH; Support,
Non-U.S. Gov't; Uracil|CH
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0305-1048
- Country of Publication
- ENGLAND
Record 34 from database: MEDLINE
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- Title
- Freeze-drying above room temperature.
- Author
- Tesconi MS; Sepassi K; Yalkowsky SH
- Address
- Department of Pharmaceutical Science, College of Pharmacy,
University of Arizona, Tucson, Arizona 85721, USA.
- Source
- J Pharm Sci, 1999 May, 88:5, 501-6
- Abstract
- This study investigates the use of solid, organic
compounds to lyophilize drugs without conventional
freeze-drying equipment. The aim of the investigation is to
find a pharmaceutically acceptable solvent or solvent
combination that is appropriate for freeze-drying on the
basis of its ability to (1) solubilize hydrophobic drugs,
(2) provide a stable environment for water-sensitive
compounds, (3) be rapidly and completely removed from the
product under vacuum, and (4) produce cakes that are readily
reconstituted. A eutectic formed from
1,1,1-trichloro-2-methyl-2-propanol (chlorobutanol)
hemihydrate and dimethyl sulfone (DMSO2) is determined to be
a suitable medium.
- Language of Publication
- English
- Unique Identifier
- 99248240
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- MeSH Heading (Major)
- Freeze Drying|*; Technology, Pharmaceutical|*
- MeSH Heading
- Particle Size; Solubility; Temperature
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-3549
- Country of Publication
- UNITED STATES
Record 35 from database: MEDLINE
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- Title
- A sulfone beta-lactam compound which acts as a beta-lactamase
inhibitor.
- Author
- Aswapokee N; Neu HC
- Address
-
- Source
- J Antibiot (Tokyo), 1978 Dec, 31:12, 1238-44
- Abstract
- CP-45,899
[3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3,2,0)heptane-2-carboxylic
acid, 4,4-dioxide [2S-(2alpha,5alpha)]] has low intrinsic
activity against most Gram-positive cocci,
Enterobacteriaceae and Pseudomonas. It inhibits Neisseria at
concentrations of 0.1 approximately 6.2 microgram/ml. The
combination of CP-45,899 and ampicillin inhibited
Staphylococcus aureus and Enterobacteriaceae resistant to
ampicillin by virtue of beta-lactamase activity. Combination
of CP-45,899 and cephalothin was synergistic less often, and
CP-45,899 did not act synergistically with carbenicillin or
ticarcillin against Pseudomonas resistant to these agents.
CP-45,899 acted synergistically with ampicillin against
Bacteroides. Synergy of CP-45,899 and ampicillin was
demonstrated at varying concentrations suggesting that it
may significantly enlarge the antibacterial activity of
ampicillin against resistant bacteria.
- Language of Publication
- English
- Unique Identifier
- 79109249
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- MeSH Heading (Major)
- beta-Lactamases|*AI; Antibiotics|*PD; Lactams|*PD;
Sulfones|*PD
- MeSH Heading
- Bacteria|EN; Drug Synergism; Microbial Sensitivity Tests;
Staphylococcus aureus|DE; Time Factors
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-8820
- Country of Publication
- JAPAN
Record 36 from database: MEDLINE
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- Title
- A reevaluation of the structure of purified tubulin in
solution: evidence for the prevalence of oligomers over
dimers at room temperature.
- Author
- Kravit NG; Regula CS; Berlin RD
- Address
-
- Source
- J Cell Biol, 1984 Jul, 99:1 Pt 1, 188-98
- Abstract
- We studied the molecular form of tubulin in solution by
ultrafiltration, nondenaturing electrophoresis, and chemical
cross-linking. Our results are not consistent with the
generally-held belief that tubulin in solution is a
110,000-mol-wt dimer. Rather, tubulin in solution consists
of small oligomers; dimers are a minority species. The small
proportion of dimers was readily apparent from
ultrafiltration experiments. We first compared the
filterability (defined as the ratio of protein concentration
in filtrate to that applied to the filter) of
phosphocellulose-purified tubulin (PC-tubulin) with aldolase
(142,000 mol wt). Using an Amicon XM 300 filter, the
filterability of PC-tubulin at room temperature and at a
concentration of 0.5 mg/ml was only 0.12, whereas under the
same conditions the filterability of aldolase was 0.60. We
determined the average effective molecular weight of tubulin
from its filterability on XM 300 filters calibrated with
standard proteins. At room temperature, PC-tubulin at 0.5
mg/ml had an effective molecular weight of approximately
300,000. This molecular weight was significantly reduced at
10 degrees C, indicating that oligomers dissociated at low
temperatures. Oligomers were also demonstrated by chemical
cross-linking using glutaraldehyde, dimethyl suberimidate,
and bis[2-(succinimidooxycarbonyoxy)ethyl] sulfone. In
addition, PC-tubulin ran as a series of discrete bands in a
nondenaturing PAGE system at alkaline pH. Quantitative
examination of the mobilities of these bands and of standard
proteins revealed that the bands represented a series of
oligomeric forms. Similar electrophoretic patterns were
observed in solutions of tubulin containing
microtubule-associated proteins (MAPs) but with a shift to a
greater proportion of higher oligomers. Nondenaturing PAGE
at pH 8.3 showed that a shift towards higher oligomers also
occurred in the absence of MAPs as the concentration of
tubulin was increased. This concentration-dependence of
oligomerization at room temperature was further demonstrated
by ultrafiltration. When solutions of PC-tubulin at
concentrations less than 0.25 mg/ml were ultrafiltered,
filterability increased as concentration decreased.
Quantitative studies of filterability following progressive
dilution or concentration showed that this process was
completely and rapidly reversible. A diffuse pattern of PC-tubulin
on nondenaturing PAGE at pH 7 was observed and is consistent
with a mixture of oligomers in rapid equilibrium.(ABSTRACT
TRUNCATED AT 400 WORDS)
- Language of Publication
- English
- Unique Identifier
- 84239980
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- MeSH Heading (Major)
- Tubulin|*AN
- MeSH Heading
- Animal; Cattle; Cross-Linking Reagents|PD;
Electrophoresis, Polyacrylamide Gel; Macromolecular Systems;
Molecular Weight; Proteins|ME; Support, U.S. Gov't, P.H.S.;
Temperature; Transferrin|PD; Ultrafiltration
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9525
- Country of Publication
- UNITED STATES
Record 37 from database: MEDLINE
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- Title
- Synthesis and in vitro antimalarial activity of sulfone
endoperoxides.
- Author
- Bachi MD; Korshin EE; Ploypradith P; Cumming JN; Xie S;
Shapiro TA; Posner GH
- Address
- Department of Organic Chemistry, Weizmann Institute of
Science, Rehovot, Israel.
- Source
- Bioorg Med Chem Lett, 1998 Apr 21, 8:8, 903-8
- Abstract
- A series of
4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+
++nonanes, carrying a variety of substituents at position-8
(4) were prepared by a short and efficient method from
R-(+)-limonene. Key reactions include thiol oxygen
cooxidation, and alkylation and acylation of a sterically
hindered tertiary alcohol compatible with the endoperoxy
functionality. Some of compounds 4, which are structurally
related to yingzhaosu A (2), were found to exhibit in vitro
antimalarial activity comparable to that of artemisinin (1)
and superior to that of arteflene (3).
- Language of Publication
- English
- Unique Identifier
- 99088675
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- MeSH Heading (Major)
- Antimalarials|CH/*CS/PD; Plasmodium falciparum|*DE;
Sulfones|CH/*CS/PD
- MeSH Heading
- Animal; Chloroquine|PD; Drugs, Chinese Herbal; Models,
Molecular; Molecular Conformation; Molecular Structure;
Peroxides; Sesquiterpenes|CH; Structure-Activity
Relationship; Support, Non-U.S. Gov't; Support, U.S. Gov't,
Non-P.H.S.; Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0960-894X
- Country of Publication
- ENGLAND
- CAS Registry/EC Number
- 0 (Antimalarials); 0 (Drugs, Chinese Herbal); 0
(Peroxides); 0 (Sesquiterpenes); 0 (Sulfones); 54-05-7 (Chloroquine)
Record 38 from database: MEDLINE
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- Title
- Sulfoxidation of thioether-containing pesticides by the
flavin-adenine dinucleotide- dependent monooxygenase of pig
liver microsomes.
- Author
- Hajjar NP; Hodgson E
- Address
-
- Source
- Biochem Pharmacol, 1982 Mar, 31:5, 745-52
- Abstract
- In the presence of NADPH and under aerobic conditions,
thioether-containing organo-phosphorus and carbamate
pesticides were oxidized by the FAD-dependent monooxygenase
(EC 1.14.13.8) purified from pig liver microsomes. The
stoichiometric relationship between NADPH and substrate
during the course of the reaction was 1:1, and the product,
in the case of disulfoton and phorate, was the sulfoxide.
The product was optically active and further oxidation to
the sulfone was not apparent. Furthermore, the sulfoxides of
disulfoton, phorate and croneton were not substrates for
this enzyme. n-Octylamine, a known cytochrome P-450
inhibitor, increased the rate of sulfoxidation reactions
catalyzed by the FAD-dependent monooxygenase.
Structure-activity relationships were investigated using
thirty-nine possible substrates. Structural changes around
the thioether sulfur that affect nucleophilicity or that
cause steric hindrance tended to decrease the sulfoxidation
rats. With phosphorodithioates, changes around the
phosphorus atom also affected oxidation of the thioether
sulfur. Although neither the thiono nor the thiol sulfur
atoms were attacked, substitution of either sulfur by oxygen
decreased sulfoxidation. Thioether-containing O, O-dimethyl
phosphorodithioates were not oxidized as readily as their O,
O-diethyl analogs. Tetram and its analogs, which contain a
teritiary amine group, were also substrates for this enzyme,
presumably forming the N-oxide.
- Language of Publication
- English
- Unique Identifier
- 82206117
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- MeSH Heading (Major)
- FAD|*PD; Insecticides, Carbamate|*ME; Insecticides,
Organophosphate|*ME; Microsomes, Liver|*EN; Oxygenases|*PD;
Sulfoxides|*ME
- MeSH Heading
- Animal; Structure-Activity Relationship; Support, U.S.
Gov't, P.H.S.; Swine
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2952
- Country of Publication
- ENGLAND
Record 39 from database: MEDLINE
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- Title
- In vivo testing of hypoxic radiosensitizers using the KHT
murine tumour assayed by the lung-colony technique.
- Author
- Rauth AM; Kaufman K
- Address
-
- Source
- Br J Radiol, 1975 Mar, 48:567, 209-20
- Abstract
- The KHT transplantable tumour of C3H mice has been used as
a model tumour for the invivo study of hypoxic cell
sensitizers. Eleven sensitizers comprising four nitrofuran
five nitrobenzene and two nitroimidazole derivatives, which
have been shown to be effective on hypoxic mammalian cells
in vitro, have been investigated. Two of these compounds,
metronidazole (2-methyl-5-nitroimidazole-1 ethanol) and
tinidazole (ethyl [2-(2'-methyl-5'-nitro-1'-imidazolyl)
ehtyl] sulfone), showed signs of hypoxic cell-sensitization
in vivo when given systemically by intraperitoneal
injections. In addition, preliminary testing of the
nitrobenzene NDPP (P-NITRO-3-DIMETHYL-PROPRIOPHENONE
HYDROCHLORIDE) INDICATED THAT WHEN IT WAS INJECTED DIRECTLY
INTO THE TUMOUR AND IRRADIATION WAS COMPLETED WITHIN TEN
MINUTES AFTER INJECTION, APPRECIABLE SENSITIZATION WAS
OBTAINED. More detailed studies indicated that both
metronidazole at 1,500 mg/kg and tinidazole at 750 mg/kg
given intraperitoneally gave an enhancement ratio of 1-5 for
a chronically hyopix cell population in this solid tumour in
air-breathing mice. Measures of plasma levels of
metronidazole and enhancement ratios obtained in the present
in vivo system seem in relative agreement with the in vitro
and in vivo results of others.
- Language of Publication
- English
- Unique Identifier
- 75147483
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- MeSH Heading (Major)
- Anoxia|*; Radiation-Sensitizing Agents|BL/*PD/TO; Sarcoma,
Experimental|AN/*RT
- MeSH Heading
- Animal; Cell Division; Cell Survival; Dose-Response
Relationship, Radiation; Kinetics; Lethal Dose 50; Lung|CY;
Male; Metronidazole|AN; Mice; Mice, Inbred C3H;
Nitrobenzenes|PD; Nitrofurans|AN/PD; Nitroimidazoles|PD;
Radiation Effects
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0007-1285
- Country of Publication
- ENGLAND
Record 40 from database: MEDLINE
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- Title
- Effects of charge, volume, and surface on binding of
inhibitor and substrate moieties to acetylcholinesterase.
- Author
- Cohen SG; Chishti SB; Elkind JL; Reese H; Cohen JB
- Address
-
- Source
- J Med Chem, 1985 Sep, 28:9, 1309-13
- Abstract
- Reversible inhibitors for acetylcholinesterase, AcChE,
have been studied. Sterically similar alcohols with
tetra-substituted uncharged beta groups, (CH3)3SiCH2CH2OH
(I), (CH3)3CCH2CH2OH (IA), and CH3S(O2)CH2CH2OH (VII), bind
similarly, KI = 3-9 mM, and each binds similarly to its
acetate substrate; cationic analogues, (CH3)3N+CH2CH2OH (IB)
and (CH3)2S+CH2CH2OH (II), bind similarly to each other, KI
= 0.4 mM, similar to Km values of their acetate substrates,
and more strongly than the uncharged alcohols by
approximately 1.5 kcal/mol. In comparisons of VII with
CH3SO2CH3, II with (CH3)3S+, and IB with (CH3)4N+,
hydroxyethyl leads to more favorable binding than methyl by
approximately 0.8 kcal/mol, despite lower hydrophobicity.
Two hydrophobic methyl groups, in comparison of IA with
butanol, and two hydrophilic sulfone O atoms, in comparison
of VII with 2-(methylthio)ethanol, increase binding
similarly, by 1.0 kcal/mol. Conversion of (CH3)3S+ to
(CH3)3S+O also improves binding. However, (CH3)3N+O- does
not bind to AcChE, and conversion of
1-(dimethylammonio)-4-pentanone and 2-(dimethylammonio)ethyl
acetate to their N-oxides, changes of identical to N+H to
identical to N+--O-, decreases binding by 1.5 kcal/mol.
Although the -COCH3 group in esters with well-binding beta
substituents makes essentially no contribution to binding
over that of the alcohols, in esters with weakly bound beta
substituents, (CH3)2N+(O-), CH3N+H2, CH3S(O), CH3CH2, and
CH3S binding is dominated by the ester -COCH3 group, with
values of Km approximately 16 mM.
- Language of Publication
- English
- Unique Identifier
- 85292983
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- MeSH Heading (Major)
- Acetylcholinesterase|*ME; Cholinesterase Inhibitors|*ME;
Ethanol|AA/*ME
- MeSH Heading
- Binding, Competitive; Butanols|ME; Chemistry, Physical;
Choline|AA/ME; Comparative Study; Dimethyl Sulfoxide|ME;
Kinetics; Structure-Activity Relationship; Sulfones|ME;
Sulfonium Compounds|ME; Support, Non-U.S. Gov't; Support,
U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.;
Trimethylsilyl Compounds|ME
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2623
- Country of Publication
- UNITED STATES
Record 41 from database: MEDLINE
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- Title
- The effects of arotinoids on rat mammary carcinogenesis.
- Author
- Hartmann HR; Bollag W
- Address
-
- Source
- Cancer Chemother Pharmacol, 1985, 15:2, 141-3
- Abstract
- The influence of two retinoids, Ro 13-6298, an arotinoid
ethyl ester, and Ro 15-1570, an arotinoid ethyl sulfone, on
rat mammary carcinogenesis was investigated. Mammary
carcinomas were induced by oral administration of 15 mg
dimethylbenz(a)anthracene (DMBA) to 50-day-old female
Sprague-Dawley rats. Oral administration of the two
retinoids significantly inhibited the development of tumors.
The number and volume of mammary neoplasms were influenced
in a dose-dependent manner.
- Language of Publication
- English
- Unique Identifier
- 85255301
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- MeSH Heading (Major)
- Antineoplastic Agents|*TU; Benzoates|*TU; Mammary
Neoplasms, Experimental|CI/PA/*PC; Retinoids|*TU
- MeSH Heading
- Animal; Body Weight|DE; Dose-Response Relationship, Drug;
Female; Rats; Rats, Inbred Strains;
9,10-Dimethyl-1,2-benzanthracene
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0344-5704
- Country of Publication
- GERMANY, WEST
Record 42 from database: MEDLINE
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- Title
- Selective inversion investigations of slow molecular
motion in solid state deuteron NMR spectroscopy.
- Author
- Brown MJ; Vold RL; Hoatson GL
- Address
- Department of Physics, College of William and Mary,
Williamsburg, VA 23187-8795, USA.
- Source
- Solid State Nucl Magn Reson, 1996 Apr, 6:2, 167-85
- Abstract
- Deuteron selective inversion experiments are reported for
polycrystalline dimethyl sulfone-d6 as a function of
temperature from 288 to 333 K. Double side-band modulation
was used to achieve efficient off-resonance
orientation-selective inversion. Fitting the selective
inversion-recovery curves to two-site jump equations yields
the motional rate. Temperature dependent jump rates,
obtained from both selective inversion and deuteron
quadrupole echo lineshapes, give an activation energy Ea =
86.5 +/- 1.4 kJ mol-1 and a frequency factor In(A) = 39.2
+/- 0.5. These values differ significantly from those of
earlier 13C lineshape studies. At 298 K, variable power
excitation was used to determine the underlying orientation
dependent homogeneous linewidth, which is predominantly
dipolar. The temperature dependence of the homogeneous
linewidth is a sensitive indicator of large angle jump
motion in the range 10(3)-10(4) s-1.
- Language of Publication
- English
- Unique Identifier
- 96379436
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- MeSH Heading (Major)
- Deuterium|*CH; Nuclear Magnetic Resonance|*MT
- MeSH Heading
- Anisotropy; Models, Chemical; Molecular Structure;
Sulfones|CH; Support, U.S. Gov't, Non-P.H.S.; Temperature;
Thermodynamics
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0926-2040
- Country of Publication
- NETHERLANDS
Record 43 from database: MEDLINE
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- Title
- Flavins inhibit human cytomegalovirus UL80 protease via
disulfide bond formation.
- Author
- Baum EZ; Ding WD; Siegel MM; Hulmes J; Bebernitz GA;
Sridharan L; Tabei K; Krishnamurthy G; Carofiglio T; Groves
JT; Bloom JD; DiGrandi M; Bradley M; Ellestad G; Seddon AP;
Gluzman Y
- Address
- Wyeth-Ayerst Research, Lederle Laboratories, Pearl River,
New York 10965, USA. BAUME@war.wyeth.com
- Source
- Biochemistry, 1996 May, 35:18, 5847-55
- Abstract
- Among the most potent inhibitors of human cytomegalovirus
protease identified by random screening of a chemical
library was 1,4-dihydro-7,8-dimethyl
6H-pyrimido[1,2-b]-1,2,4,5-tetrazin-6-one (1) (PTH2). The
oxidized form (2), PT, which is present in solutions of
PTH2, was shown to be the actual inhibitory species which
irreversibly inactivates the protease; recycling of PTH2 by
dissolved oxygen results in complete inhibition of the
protease at substoichiometric amounts of compound. No
evidence for a covalent adduct between the protease and the
inhibitor was obtained, and protease activity was restored
by incubation of the inactivated enzyme with the reducing
agent bismercaptoethyl sulfone, suggesting that disulfide
bond formation was responsible for the observed inhibition.
The five cysteines of the protease are normally in the
reduced state; analysis of tryptic peptides from inhibited
protease indicated that disulfide bonds Cys84-Cys87 and
Cys138-Cys161 were formed. Using site-directed mutagenesis,
the disulfide pair induced between Cys138 and Cys161
disulfide is dependent upon interaction of PT with the
protease and does not form spontaneously, unlike that of the
Cys84-Cys87 pair which can form in the absence of inhibitor.
The inhibitor's redox chemistry is analogous to that of
flavin, and, in fact, flavin inhibits the protease by the
same mechanism, causing formation of a disulfide bond
between Cys138 and Cys161. That the cysteines are
dispensable, but can regulate protease activity by formation
of a unique disulfide pair, suggests a plausible mechanism
for control of proteolysis during the viral life cycle.
- Language of Publication
- English
- Unique Identifier
- 96216858
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- MeSH Heading (Major)
- Cytomegalovirus|*EN/GE; Dacarbazine|*AA/PD; Flavins|*PD;
Peptide Peptidohydrolases|*CH/GE/*ME; Protease
Inhibitors|*PD; Viral Proteins|*CH/GE/*ME
- MeSH Heading
- Base Sequence; Binding Sites; Chromatography, High
Pressure Liquid; Cysteine|CH; Disulfides|CH; DNA Primers|GE;
DNA, Viral|GE; Human; Molecular Sequence Data; Molecular
Structure; Mutagenesis, Site-Directed; Oxidation-Reduction;
Point Mutation
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0006-2960
- Country of Publication
- UNITED STATES
Record 44 from database: MEDLINE
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- Title
- Dynamic 2H nuclear magnetic resonance of rotating solids.
- Author
- Weintraub O; Vega S
- Address
- Chemical Physics Department, Weizmann Institute of
Science, Rehovot, Israel.
- Source
- Solid State Nucl Magn Reson, 1995 Aug, 4:6, 341-51
- Abstract
- The sensitivity of one-dimensional dynamic magic-angle
spinning (MAS) and off-MAS 2H nuclear magnetic resonance
spectra to changes in the parameters of jump-type molecular
motions is studied. The Floquet theory approach is used to
simulate spectra of spins with I = 1, which are involved in
exchange processes in rotating solids. The solution of the
Bloch-McConnell equations for rotating samples are derived
and some simulated frequency spectra are shown. The
dependence of the lineshapes of the center and sidebands of
the MAS and off-MAS spectra on the exchange parameters are
discussed. Experimental results of 2H spectra of
perdeuterated dimethyl sulfone, obtained in the temperature
range 20-55 degrees C, are demonstrated. The methyl groups
in this molecule undergo pi flips at rates that can be
detected by MAS and off-MAS NMR. The shapes of the
experimental sidebands are compared with simulated results.
- Language of Publication
- English
- Unique Identifier
- 96061841
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- MeSH Heading (Major)
- Computer Simulation|*; Motion|*; Nuclear Magnetic
Resonance|*MT
- MeSH Heading
- Deuterium; Mathematics; Models, Chemical; Rotation;
Software; Sulfones|CH
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0926-2040
- Country of Publication
- NETHERLANDS
Record 45 from database: MEDLINE
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- Title
- Affinity labeling of the sialoglycopeptide antimitogen
receptor.
- Author
- Sharifi BG; Johnson TC
- Address
- Division of Biology, Kansas State University, Manhattan
66506.
- Source
- J Biol Chem, 1987 Nov, 262:32, 15752-5
- Abstract
- An 18-kDa 125I-sialoglycopeptide growth inhibitor was
covalently cross-linked to its binding site on intact
cultured Swiss 3T3 cells by three bifunctional cross-linkers
with short (dimethyl adipimate), medium (disuccinimidyl
suberate), and long
(bis(2-succinimidooxycarbonyloxyethyl)sulfone) chain
lengths. Analysis by sodium dodecyl sulfate-polyacrylamide
gel electrophoresis and autoradiography demonstrated a band
of Mr approximately 168,000 regardless of which cross-linker
was used. The labeling of this band was specific in that it
was prevented by excess unlabeled inhibitor and the apparent
molecular weight of the cross-linked receptor-ligand complex
was unchanged by treatment with reducing agent. The
efficiency of the cross-linking was increased by increasing
pH, and the extent of covalent cross-linking was dependent
on the concentration of the bifunctional reagent. Octyl
glucoside and sodium dodecyl sulfate were effective in
solubilizing the receptor while Triton X-100 did not extract
the receptor from the plasma membrane. These observations
suggest that the 168-kDa binding species represents the
125I-sialoglycopeptide cross-linked to a specific plasma
membrane receptor and that the receptor does not appear to
contain interchain disulfide bonds.
- Language of Publication
- English
- Unique Identifier
- 88058920
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- MeSH Heading (Major)
- Affinity Labels|*ME; Receptors, Immunologic|*ME;
Sialoglycoproteins|AI/*ME
- MeSH Heading
- Animal; Cross-Linking Reagents|PD; Disulfides|AN;
Glucosides; Hydrogen-Ion Concentration; Molecular Weight;
Sodium Dodecyl Sulfate; Solubility; Support, Non-U.S. Gov't;
Support, U.S. Gov't, P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
Record 46 from database: MEDLINE
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- Title
- 1-((7,7-Dimethyl-2(S)-(2(S)-amino-4-(methylsulfonyl)butyramido)bicyclo
[2.2.1]-heptan-1(S)-yl)methyl)sulfonyl)-4-(2-methylphenyl)piperaz
ine (L-368,899): an orally bioavailable, non-peptide
oxytocin antagonist with potential utility for managing
preterm labor.
- Author
- Williams PD; Anderson PS; Ball RG; Bock MG; Carroll L;
Chiu SH; Clineschmidt BV; Culberson JC; Erb JM; Evans BE; et
al
- Address
- Department of Medicinal Chemistry, Merck Research
Laboratories, West Point, Pennsylvania 19486.
- Source
- J Med Chem, 1994 Mar, 37:5, 565-71
- Abstract
- Modifications to the previously reported
spiroindenylpiperidine camphor-sulfonamide oxytocin (OT)
antagonist L-366,509 have produced a new series of o-tolylpiperazine
(TP) camphor-sulfonamides. A number of analogues in the TP
series that incorporate a modified or unmodified
L-methionine sulfone amide at the C2 endo position on the
camphor ring exhibit high affinity for OT receptors (IC50 =
1.3-15 nM) and good selectivity for binding to OT versus
arginine vasopressin V1a and V2 receptors. Several of these
analogues were additionally characterized as potent
antagonists of OT-stimulated contractions of the isolated
and/or in situ rat uterus. Compound 7 (L-368,899) exhibited
the best overall profile of OT receptor affinity (IC50 = 8.9
nM, rat uterus; 26 nM, human uterus), potency for inhibition
of OT-stimulated contractions of the isolated rat uterus
(pA2 = 8.9) and in situ rat uterus (AD50 = 0.35 mg/kg after
intravenous (i.v.) administration and 7.0 mg/kg after
intraduodenal administration), aqueous solubility (3.7 mg/mL
at pH 5.0), and oral bioavailability in several species (35%
(rat), 25% (dog), and 21% (chimpanzee) as estimated from
radioreceptor determination of drug levels in plasma after
oral and i.v. dosing). On the basis of these favorable
properties, 7 has begun clinical testing for use as an oral
and i.v. tocolytic agent. Molecular modeling alignment
studies have provided support for the hypothesis that the TP
camphor-sulfonamide portion of the non-peptide structures
may serve as a mimetic of the important D-AA2-Ile3 dipeptide
(AA = aromatic amino acid) found in many potent OT
antagonists from the cyclic hexapeptide and OT analogue
structural classes.
- Language of Publication
- English
- Unique Identifier
- 94172599
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- MeSH Heading (Major)
- Bornanes|*CH/PD/PK; Labor, Premature|*DT; Oxytocin|*AI/PD;
Piperazines|*CH/PD/PK; Tocolytic Agents|*CH/PD/PK
- MeSH Heading
- Animal; Biological Availability; Crystallography, X-Ray;
Dogs; Female; Human; Macaca mulatta; Models, Molecular;
Molecular Structure; Pregnancy; Rats; Receptors, Oxytocin|ME;
Structure-Activity Relationship; Uterine Contraction|DE
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0022-2623
- Country of Publication
- UNITED STATES
Record 47 from database: MEDLINE
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- Title
- Dimethyl sulfone (DMSO2) in the treatment of interstitial
cystitis.
- Author
- Childs SJ
- Address
- Department of Surgery, University of Alabama-Tuscaloosa.
- Source
- Urol Clin North Am, 1994 Feb, 21:1, 85-8
- Abstract
- DMSO2 is one alternative for treating interstitial
cystitis. Research with this compound is very limited, but
side effects have been negligible. The drug may hold promise
for interstitial cystitis patients, as well as those
suffering from painful bladder (urethral) syndrome.
- Language of Publication
- English
- Unique Identifier
- 94112755
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- MeSH Heading (Major)
- Anti-Inflammatory Agents, Topical|*TU; Cystitis|*DT;
Sulfones|*TU
- MeSH Heading
- Adult; Case Report; Female; Human
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0094-0143
- Country of Publication
- UNITED STATES
Record 48 from database: MEDLINE
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- Title
- Mechanism of potentiation of BPMC toxicity by fenthion
pretreatment in mice.
- Author
- Miyaoka T; Tsuda S; Shirasu Y
- Address
-
- Source
- J Pharmacobiodyn, 1986 Sep, 9:9, 697-703
- Abstract
- The mechanism of potentiation of 2-sec-butylphenyl N-methylcarbamate
(BPMC) toxicity by O,O-dimethyl
O-(3-methyl-4-methylthiophenyl) phosphorothioate (fenthion)
in mice was investigated in relation to BPMC metabolism in
the liver. Simultaneous administration of BPMC and either
one of the thiophosphates (fenthion, its sulfoxide and
sulfone) in a dose of 1/40 of its LD50 resulted in a 2- to
3-fold potentiation. On the other hand, one hour
pretreatment with these thiophosphates in the same dose
resulted in a 7- to 9-fold potentiation of BPMC toxicity,
but that with fenthion oxon resulted in only a 2-fold
potentiation. Plasma levels of BPMC were significantly
increased by pretreatment with the thiophosphates, but not
by the oxon. In an in vitro study, an inhibition of hepatic
microsomal metabolism of BPMC and a decrease of cytochrome
P-450 content by thiophosphates were observed at the
concentration of 10 microM, but not by 25 microM of oxon. In
an in vivo study, an inhibition of hepatic microsomal
metabolism of BPMC, aminopyrine and aniline by the
thiophosphates pretreatment were observed in doses of 1/40
of their LD50's, but not by the oxon in doses of up to 4/10
of its LD50. Cytochrome P-450 content was decreased by the
thiophosphates in doses of 4/10 of their LD50's, but not by
the oxon. These results suggested that the inhibition of
BPMC metabolism might be, at least in part, the mechanism
for the fenthion-induced potentiation of BPMC toxicity and
that desulfuration of fenthion might be responsible for the
inhibition of BPMC metabolism.
- Language of Publication
- English
- Unique Identifier
- 87086195
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- MeSH Heading (Major)
- Carbamates|*ME/TO; Fenthion|AA/*PD; Insecticides,
Carbamate|*ME/TO; Microsomes, Liver|DE/*ME
- MeSH Heading
- Animal; Drug Synergism; In Vitro; Lethal Dose 50; Male;
Mice; Mice, Inbred ICR
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0386-846X
- Country of Publication
- JAPAN
Record 49 from database: MEDLINE
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- Title
- Guinea pig liver aldehyde oxidase as a sulfoxide reductase:
its purification and characterization.
- Author
- Yoshihara S; Tatsumi K
- Address
-
- Source
- Arch Biochem Biophys, 1985 Oct, 242:1, 213-24
- Abstract
- Guinea pig aldehyde oxidase was purified about 120-fold at
a yield of 26% from liver cytosol by sequential column
chromatography using DEAE-cellulose, FMN-Sepharose 4B, and
Sephacryl S-300. The purified enzyme showed many
similarities with the rabbit liver aldehyde oxidase reported
by other workers with respect to its absolute spectra,
molecular weight, and cofactor compositions of molybdenum,
FAD, and nonheme iron. This enzyme efficiently utilized
2-hydroxypyrimidine and benzaldehyde as electron donors
while N1-methylnicotinamide was 40 times less effective than
2-hydroxypyrimidine. Diphenyl sulfoxide was reduced
anaerobically to diphenyl sulfide in the presence of
electron donors. This activity was highly susceptible to SKF
525-A as well as the known inhibitors for aldehyde oxidase
such as menadione, estradiol, and potassium cyanide. This
enzyme also reduced dibenzyl sulfoxide, phenothiazine
sulfoxide, D-biotin methyl ester d-sulfoxide, and quinoline
N-oxide, but not L-methionine sulfoxide, dimethyl sulfoxide,
D-biotin methyl ester l-sulfoxide, and D-biotin d- and l-sulfoxides,
as well as diphenyl sulfone. These results indicate that
aldehyde oxidase in guinea pig liver functions as a
sulfoxide reductase with selective substrate specificity
under anaerobic conditions.
- Language of Publication
- English
- Unique Identifier
- 86024281
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- MeSH Heading (Major)
- Aldehyde Oxidoreductases|*IP; Liver|*EN; Oxidoreductases|*IP
- MeSH Heading
- Animal; Chromatography, DEAE-Cellulose; Chromatography,
Gel; Dithiothreitol|PD; Estradiol|PD; FAD|ME; Guinea Pigs;
Molecular Weight; Molybdenum|ME; Potassium Cyanide|PD;
Proadifen|PD; Support, Non-U.S. Gov't; Vitamin K|PD
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0003-9861
- Country of Publication
- UNITED STATES
Record 50 from database: MEDLINE
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- Title
- gamma-Glutamyl amino acids. Transport and conversion to
5-oxoproline in the kidney.
- Author
- Bridges RJ; Meister A
- Address
-
- Source
- J Biol Chem, 1985 Jun, 260:12, 7304-8
- Abstract
- Transport of gamma-glutamyl amino acids, a step in the
proposed glutathione-gamma-glutamyl transpeptidase-mediated
amino acid transport pathway, was examined in mouse kidney.
The transport of gamma-glutamyl amino acids was demonstrated
in vitro in studies on kidney slices. Transport was followed
by measuring uptake of 35S after incubation of the slices in
media containing gamma-glutamyl methionine [35S]sulfone. The
experimental complication associated with extracellular
conversion of the gamma-glutamyl amino acid to amino acid
and uptake of the latter by slices was overcome by using
5-oxoproline formation (catalyzed by intracellular gamma-glutamyl-cyclotransferase)
as an indicator of gamma-glutamyl amino acid transport. This
method was also successfully applied to studies on transport
of gamma-glutamyl amino acids in vivo. Transport of gamma-glutamyl
amino acids in vitro and in vivo is inhibited by several
inhibitors of gamma-glutamyl transpeptidase and also by high
extracellular levels of glutathione. This seems to explain
urinary excretion of gamma-glutamylcystine by humans with
gamma-glutamyl transpeptidase deficiency and by mice treated
with inhibitors of this enzyme. Mice depleted of glutathione
by treatment with buthionine sulfoximine (which inhibits
glutathione synthesis) or by treatment with
2,6-dimethyl-2,5-heptadiene-4-one (which effectively
interacts with tissue glutathione) exhibited significantly
less transport of gamma-glutamyl amino acids than did
untreated controls. The findings suggest that intracellular
glutathione functions in transport of gamma-glutamyl amino
acids. Evidence was also obtained for transport of gamma-glutamyl
gamma-glutamylphenylalanine into kidney slices.
- Language of Publication
- English
- Unique Identifier
- 85207764
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- MeSH Heading (Major)
- Amino Acids|*ME; Kidney|*ME; Pyrrolidinones|*BI;
Pyrrolidonecarboxylic Acid|*BI
- MeSH Heading
- Animal; Biological Transport; Glutamates|ME;
Glutathione|AI/ME; In Vitro; Kinetics; Male; Mice; Mice,
Inbred Strains; Structure-Activity Relationship; Substrate
Specificity; Sulfur Radioisotopes; Support, U.S. Gov't,
P.H.S.
- Publication Type
- JOURNAL ARTICLE
- ISSN
- 0021-9258
- Country of Publication
- UNITED STATES
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