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PubMed1985

Role of 3,5-dichlorophenyl methyl sulfone, a metabolite of m-dichlorobenzene, in the induction of hepatic microsomal drug-metabolizing enzymes by m-dichlorobenzene in rats.

The increases in the hepatic microsomal aminopyrine N-demethylase activity and in the content of cytochrome P-450 produced by m-dichlorobenzene (m-DCB) occurred after increases in the hepatic concentration of 3,5-dichlorophenyl methyl sulfone, a minor metabolite. The extent of increases in aminopyrine N-demethylase activity and in the content of cytochrome P-450 at 48 hr after po administration of 200 mg/kg (1.36 mmol/kg) of m-DCB was almost equal to that 72 hr after the ip administration of 25 mumol/kg of the sulfone (Kimura et al., 1983). m-DCB in liver was not detectable at that time, and the concentration of sulfone was 63 to 70% of that 48 to 72 hr after the ip administration of 50 mumol/kg of sulfone. Administration of m-DCB (200 mg/kg) produced a significant reduction in hexobarbital sleeping time, but this reduction was less than that produced by administration of the sulfone (50 mumol/kg). The protein band patterns by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the microsomes from rats treated with the sulfone and m-DCB were similar to those of phenobarbital-treated rats but were different from those of 3-methylcholanthrene-treated rats. The sulfone showed type I interaction with the cytochrome P-450 (Ks, 0.17 mM). The sulfone was formed from the sulfide but reduction of the sulfone was not observed when it was incubated in a hepatic microsomal preparation. The pattern of induction by the sulfone and m-DCB was similar to that by phenobarbital and differed from that by 3-methylcholanthrene. From these results, 3,5-dichlorophenyl methyl sulfone is considered to be a major contributing factor of the inducing activity of m-DCB and to be a potent phenobarbital-like inducer.

Aminopyrine N-Demethylase↗
PubMed2003

Unexpected differences in the alpha-halogenation and related reactivity of sulfones with perhaloalkanes in KOH-t-BuOH.

Most alkyl phenyl sulfones are readily alpha-chlorinated with CCl(4) and alpha-brominated with CBrCl3 in KOH-t-BuOH via radical-anion radical pair (RARP) reactions. While isopropyl mesityl sulfone (4) is easily alpha-chlorinated with CCl(4), it was completely recovered when treated with the more reactive CBrCl3. Subsequent investigations showed the latter result to be due to the poor acidity of 4 together with the rapid depletion of CBrCl3 and KOH by their reaction with each other, and led to a variety of other important results. 4-Hydroxyphenyl isopropyl sulfone (6) is unreactive with either CCl4 or CBrCl3 in KOH-t-BuOH, its phenoxide anion strongly reducing the electronegativity of the sulfonyl group, thereby inhibiting alpha-anion formation. This effect is reversed by the electron-withdrawing influence of two alpha-phenyls, so that benzhydryl 4-hydroxyphenyl sulfone (8) is readily alpha-halogenated in KOH-t-BuOH with CCl4 or CBrCl3. On further contact with KOH-t-BuOH the alpha-halogenated sulfones from 8 are decomposed into benzophenone and phenol. While the alpha-halogenated derivatives of 4-methoxyphenyl benzhydryl sulfone (9) are stable to base, they are decomposed even under mildly acidic conditions into 4-methoxyphenyl 4-methoxybenzenethiolsulfonate (9c), phenol, and benzophenone. Mono-alpha-halogenation of benzyl phenyl sulfone (10) enhances the rate of the subsequent halogenation, so that alpha,alpha-dihalogenation is attained while much substrate is still present and the mono-alpha-halogenated product is not detected. The ease of reductive debromination of alpha-bromo sulfones with Cl3C- was correlated with the stability of the formed alpha-anions, explaining the success with alpha-bromobenzylic sulfones but failure with alpha-bromoalkyl sulfones. In the presence of air and the absence of competing halogenation, formation of the alpha-anions of alkyl aryl sulfones is quickly accompanied by oxidative cleavage by atmospheric O2, leading to the formation of arenesulfonyl alcohols, arenesulfonyl halides, and haloarenes.

Journal Article↗
PubMed2003

Synthesis and anti-HIV activity of sulfonated amino ribofuranans.

New sulfonated amino ribofuranans were synthesized to elucidate the relationship between structure and specific biological activities such as anti-HIV and blood anticoagulant activities. The synthesis was performed by sulfonation of copolymers having various proportion of (1 --> 5)-alpha-D-ribofuranosidic unit. The sulfonation with piperidine N-sulfonic acid produced the sulfonated amino ribofuranans in high yield. The anti-HIV activity of sulfonated 3-amino-3-deoxy-(1 --> 5)-alpha-D-ribofuranan showed more potent by increasing the degree of sulfonation and the average molecular weights. This activity was almost equal to the activities of sulfonated ribofuranans and ribopyranans reported before in spite of low molecular weight. The blood anticoagulant activities was observed at 36-48 mg/units, more potent than standard dextran sulfonate, 22.7 mg/units. In addition, the blood anticoagulant activities of sulfamide-copolysaccharide consisting various proportion of (1 --> 5)-alpha-D-ribofuranan units were potentiated by increasing sulfonated amino-ribofuranan units from 13 to 21 mg/units.

Anti-HIV Agents↗
PubMed1993

A natural isolate of Pseudomonas maltophila which degrades aromatic sulfonic acids.

A natural isolate, designated BSA56, which was originally selected for growth with benzene sulfonic acid as sole carbon and energy source, was identified as a strain of Pseudomonas maltophila. Strain BSA56 grew on a wide range of aromatic sulfonic acids and was shown to release sulfite from benzene sulfonic acid and 2-naphthalene sulfonic acid. Although it also grew on toluene sulfonic acid and pyridine sulfonic acid, no significant sulfite release was observed with these substrates. Release of sulfite from benzene sulfonic acid was greatly promoted by the presence of glycerol. The ability to release sulfite was induced by growth in the presence of benzene sulfonic acid and was repressed almost entirely by substrates allowing rapid growth such as acetate. Strain BSA56 grew better at 30 degrees C than 37 degrees C on most aromatic substrates, but the reverse was true for most aromatic sulfonates. Several mutants of BSA56 were isolated with defects in benzoate, salicylate, or gentisate metabolism. However, all these mutants retained the ability to degrade the aromatic sulfonates.

Benzenesulfonates↗
PubMed1997

Effect of N-Sulfonation on the Colloidal and Liquid Crystal Behavior of Chitin Crystallites

Chitin crystallites were heterogeneously N-sulfonated in an aqueous medium using triethylamine/sulfur trioxide (TEA/SO3) or pyridine/sulfur trioxide. The extent of N-sulfonation of the crystallites has been controlled by the amount of TEA/SO3 added in the reaction. The concentration of sulfur in the crystallites after N-sulfonation was quantified using conductimetric titration and elemental analysis. The ratio of N-sulfonated amino groups to amino groups (S/N) was calculated based on the titration data. The presence of N-S bonds assumed to be at crystallite surfaces was demonstrated by X-ray photoelectron spectroscopy (XPS). After N-sulfonation, the crystallites have two ionizable groups at their surface: -NH3+ and -NHSO3H(Na). The former is pH dependent. The colloidal properties of the N-sulfonated crystallites having different S/N were investigated by plotting the zeta potential as a function of the pH of the suspension. The isoelectric point was found to change with the level of N-sulfonation. Transmission electron microscopy shows that the aggregation of crystallites depends strongly on the extent of N-sulfonation. Above a certain concentration, the original chitin crystallites form tactoids (chiral nematic domains) in an aqueous medium. This phenomenon was not observed for the crystallites with a low extent of surface N-sulfonation (below 70%). At about 80% N-sulfonation, the formation of tactoids was once again observed. Copyright 1997Academic Press

Journal Article↗
PubMed1995

Hapten-induced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid.

Hapten-induced colitis is a widely used model for the study of the intestinal inflammation and for the testing of novel therapies. However, the hapten utilized in this model, trinitrobenzene sulfonic acid, is difficult to obtain in some countries. We therefore compared this hapten to two structurally related haptens to determine if they could be substituted for trinitrobenzene sulfonic acid in terms of inducing chronic colitis in the rat. Rats received one of the three haptens intracolonically, and the severity of colonic inflammation was assessed 3 and 14 days later. Dinitrobenzene sulfonic acid produced colonic inflammation and ulceration that was indistinguishable from that induced by trinitrobenzene sulfonic acid at both time points. On the other hand, dinitrochlorobenzene produced acute colitis (3 days postadministration), but by Day 14 this inflammation had subsided. Dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produced comparable levels of granulocyte infiltration into the colon (as measured by tissue myeloperoxidase activity and histology) at both time points. These studies suggest that for studies of up to at least 2 weeks in duration, dinitrobenzene sulfonic acid and trinitrobenzene sulfonic acid produce comparable levels of colonic inflammation. Dinitrobenzene sulfonic acid therefore offers a useful and less expensive alternative to trinitrobenzene sulfonic acid.

Animals↗
PubMed2004

Synthesis, characterization, and crystal structures of three new divalent metal carboxylate-sulfonates with a layered and one-dimensional structure.

Hydrothermal reactions of 5-sulfoisophthalic acid (HO(3)SC(6)H(3)-1,3-(CO(2)H)(2), H(3)L) with M(II) carbonate (or oxide) and 4,4'-bipyridine (4,4'-bipy) (or 2,2'-bipyridine, 2,2'-bipy) resulted in three new metal carboxylate-sulfonate hybrids, namely, [CdL(H-4,4'-bipy)] (1) and [Cd(3)L(2)(2,2-bipy)(4)(H(2)O)(2)].2H(2)O (2) with layered structures and [ZnL(H-4,4'-bipy)(H(2)O)].2H(2)O (3), whose structure features a one-dimensional double chain. The cadmium(II) ion in complex 1 is seven-coordinated by five carboxylate oxygen atoms and one sulfonate oxygen atom from four ligands and a unidentate 4,4'-bipyridine. The interconnection of the cadmium(II) ions through bridging carboxylate-sulfonate ligands resulted in the formation of a <002> double layer with the bipyridyl rings orientated toward the interlayer space. Complex 2 has a different layered structure. Cd(1) is seven-coordinated by two bidentate chelating carboxylate groups from two ligands, a bidentate chelating 2,2'-bipy and an aqua ligand, and Cd(2) is octahedrally coordinated by two bidentate chelating 2,2'-bipy's, a sulfonate oxygen, and an aqua ligand. The coordination geometry around Cd(3) is similar to that of Cd(1) with the aqua ligand being replaced by an oxygen atom from the sulfonate group. The carboxylate-sulfonate ligand acts as pentadentate ligand, bridging with three cadmium(II) ions. The bridging of cadmium(II) ions through the carboxylate-sulfonate ligands resulted in the formation of <006> and <003> layers; the 2,2'-bipy molecules and [Cd(2)(2,2'-bipy)(2)(H(2)O)] cations are orientated to the interlayer space. Complex 3 features a 1D metal carboxylate-sulfonate double chain along the diagonal of the a- and b-axes. The zinc(II) ion is octahedrally coordinated by four carboxylate O atoms from three ligands, a unidentate 4,4'-bipy, and an aqua ligand. Each pair of zinc(II) ions is bridged by two carboxylate groups from two ligands to form a dimer, and such dimeric units are interconnected by bridging ligands to form a double chain. The sulfonate group of the carboxylate sulfonate ligand remains noncoordinated and forms a number of hydrogen bonds with aqua ligands as well as lattice water molecules.

Journal Article↗
PubMed1993

Metabolism of sulfonate analogs of ursodeoxycholic acid and their effects on biliary bile acid composition in hamsters.

The metabolism of sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate was studied in hamsters. In bile fistula animals these sulfonate analogs of ursodeoxycholic acid were absorbed mainly from the terminal ileum and secreted rapidly into the bile without biotransformation or conjugation. After oral administration, the sulfonate analogs were excreted in the feces at the same rate as chenodeoxycholic acid and its metabolic products. The intestinal microorganisms transformed chenodeoxycholic acid largely into lithocholic acid; the sulfonate analogs were completely resistant to biotransformation. After a 2-week feeding period, the sulfonate analogs of ursodeoxycholic acid accounted for 24.0% and 16.9% of total biliary bile acids. These sulfonates did not affect the proportions of the natural bile acids in the bile, and the ratio of glycine-conjugated bile acids to taurine-conjugated bile acids was not altered by feeding the sulfonates. In contrast, when ursodeoxycholic acid was fed, the proportions of the natural bile acids and the glycine/taurine ratio were changed. These results suggest that the sulfonate analogs had no profound effect on endogenous bile acid metabolism and did not cause a depletion of the hepatic taurine pool during enterohepatic circulation. The sulfonates had no effect on intestinal cholesterol absorption and serum cholesterol levels.

Animals↗
PubMed2004

Peptidyl allyl sulfones: a new class of inhibitors for clan CA cysteine proteases.

A new series of peptidyl allyl sulfone inhibitors was discovered while trying to synthesize epoxy sulfone inhibitors from vinyl sulfones using basic oxidizing conditions. The various dipeptidyl allyl sulfones were evaluated with calpain I, papain, cathepsins B and L, cruzain and rhodesain and found to be potent inhibitors. In comparison to the previously developed class of vinyl sulfone inhibitors, the novel dipeptidyl allyl sulfones were more potent inhibitors than the corresponding dipeptidyl vinyl sulfones. It was observed that the stereochemistry of the vinyl sulfone precursor played a role in the potency of the dipeptidyl allyl sulfone inhibitor.

Animals↗
PubMed1998

Conformational changes and anticoagulant activity of chondroitin sulfate following its O-sulfonation.

Chondroitin sulfate from bovine tracheal cartilage, with the basic structure (4-O-sulfo-D-GalpNAc beta-1-->4-D-GlcpA)n, was chemically modified by O-sulfonation. Depending on the reaction conditions, the products showed a different degree of O-sulfonation. A fully O-sulfonated chondroitin sulfate, having no free hydroxyl groups, and a sulfo ester group:disaccharide unit ratio of 4.0 was prepared. This chondroitin sulfate derivative was shown by 1H NMR spectroscopy to have a uronate residue with an altered conformation. Usually, the uronate residue in chondroitin sulfate resides in the 4C1 form. Fully O-sulfonated chondroitin sulfate had an uronate residue in the 1C4 form at 30 degrees C, similar to the preferred conformation of the 2-O-sulfo-iduronate residue most commonly found in heparin. The 2S0 form of the uronate residue was also found in fully O-sulfonated chondroitin sulfate at 60 degrees C. The anti-factor IIa activity of fully O-sulfonated chondroitin sulfate was 40 units/mg. This value is similar to the activities reported for various low-molecular-weight heparins, and substantially higher than those previously reported for partially O-sulfonated chondroitin sulfates having an average sulfate group/disaccharide unit of 2.5 to 3.3. The anti-factor Xa activity of the fully O-sulfonated chondroitin sulfate was 12 units/mg. This value is considerably lower than the activities reported for various low-molecular-weight heparins, consistent with the critical importance of an antithrombin III pentasaccharide binding site for anti-factor Xa activity. These findings suggest that the conformational change of glucuronic acid residue in chondroitin sulfate resulting from its full O-sulfonation can result in enhanced anticoagulant activity, particularly as measured by anti-factor IIa assay.

Animals↗
PubMed1998

Mechanisms for selective toxicity of fipronil insecticide and its sulfone metabolite and desulfinyl photoproduct.

Fipronil, an N-phenylpyrazole with a trifluoromethylsulfinyl substituent, initiated the second generation of insecticides acting at the gamma-aminobutyric acid (GABA) receptor to block the chloride channel. The first generation includes the polychlorocycloalkanes alpha-endosulfan and lindane. In this study, we examine the mechanisms for selective toxicity of the sulfoxide fipronil and its sulfone metabolite and desulfinyl photoproduct relative to their target site interactions in vitro and ex vivo and the importance in fipronil action of biooxidation to the sulfone. Differences in GABA receptor sensitivity, assayed by displacement of 4'-ethynyl-4-n-[2, 3-3H2]propylbicycloorthobenzoate ([3H]EBOB) from the noncompetitive blocker site, appear to be a major factor in fipronil being much more toxic to the insects (housefly and fruit fly) than to the vertebrates (humans, dogs, mice, chickens, quail, and salmon) examined; in insects, the IC50s range from 3 to 12 nM for fipronil and its sulfone and desulfinyl derivatives, while in vertebrates, the IC50 average values are 1103, 175, and 129 nM for fipronil, fipronil sulfone, and desulfinyl fipronil, respectively. The insect relative to the vertebrate specificity decreases in the following order: fipronil > lindane > desulfinyl fipronil > fipronil sulfone > alpha-endosulfan. Ex vivo inhibition of [3H]EBOB binding in mouse brain is similar for fipronil and its sulfone and desulfinyl derivatives at the LD50 dose, but surprisingly, at higher doses fipronil can be lethal without detectably blocking the [3H]EBOB site. The P450 inhibitor piperonyl butoxide, acting in houseflies, increases the metabolic stability and effectiveness of fipronil and the sulfone but not those of the desulfinyl compound, and in mice it completely blocks the sulfoxide to sulfone conversion without altering the poisoning. Thus, the selective toxicity of fipronil and fipronil-derived residues is due in part to the higher potency of the parent compound at the insect versus the mammalian GABA receptor but is also dependent on the relative rates of conversion to the more persistent and less selective sulfone metabolite and desulfinyl photoproduct.

Animals↗
PubMed2002

Sulfonation and molecular action.

The sulfonation of endogenous molecules is a pervasive biological phenomenon that is not always easily understood, and although it is increasingly recognized as a function of fundamental importance, there remain areas in which significant cognizance is still lacking or at most minimal. This is particularly true in the field of endocrinology, in which the sulfoconjugation of hormones is a widespread occurrence that is only partially, if at all, appreciated. In the realm of steroid/sterol sulfoconjugation, the discovery of a novel gene that utilizes an alternative exon 1 to encode for two sulfotransferase isoforms, one of which sulfonates cholesterol and the other pregnenolone, has been an important advance. This is significant because cholesterol sulfate plays a crucial role in physiological systems such as keratinocyte differentiation and development of the skin barrier, and pregnenolone sulfate is now acknowledged as an important neurosteroid. The sulfonation of thyroglobulin and thyroid hormones has been extensively investigated and, although this transformation is better understood, there remain areas of incomplete comprehension. The sulfonation of catecholamines is a prevalent modification that has been extensively studied but, unfortunately, remains poorly understood. The sulfonation of pituitary glycoprotein hormones, especially LH and TSH, does not affect binding to their cognate receptors; however, sulfonation does play an important role in their plasma clearance, which indirectly has a significant effect on biological activity. On the other hand, the sulfonation of distinct neuroendocrine peptides does have a profound influence on receptor binding and, thus, a direct effect on biological activity. The sulfonation of specific extracellular structures plays an essential role in the binding and signaling of a large family of extracellular growth factors. In summary, sulfonation is a ubiquitous posttranslational modification of hormones and extracellular components that can lead to dramatic structural changes in affected molecules, the biological significance of which is now beginning to be appreciated.

Amino Acid Sequence↗
PubMed2006

Effective detection of peptides containing cysteine sulfonic acid using matrix-assisted laser desorption/ionization and laser desorption/ionization on porous silicon mass spectrometry.

Cysteine sulfonic acid-containing peptides, being typical acidic peptides, exhibit low response in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. In this study, matrix conditions and the effect of diammonium hydrogencitrate (DAHC) as additive were investigated for ionization of cysteine sulfonic acid-containing peptides in MALDI. A matrix-free ionization method, desorption/ionization on porous silicon (DIOS), was also utilized to evaluate the effect of DAHC. When equimolar three-component mixtures of peptides carrying free cysteine, cysteine sulfonic acid, and carbamidomethyl cysteine were measured by MALDI using a common matrix, alpha-cyano-4-hydroxycinnamic acid (CHCA), no signal corresponding to cysteine sulfonic acid-containing peptide could be observed in the mass spectrum. However, by addition of DAHC to CHCA, the peaks of cysteine sulfonic acid-containing peptides were successfully observed, as well as when using 2,4,6-trihydroxyacetophenone (THAP) and 2,6-dihydroxyacetophenone with DAHC. In the DIOS mass spectra of these analytes, the use of DAHC also enhanced the peak intensity of the cysteine sulfonic acid-containing peptides. On the basis of studies with these model peptides, tryptic digests of oxidized peroxiredoxin 6 were examined as a complex peptide mixture by MALDI and DIOS. In MALDI, the peaks of cysteine sulfonic acid-containing peptides were observed when using THAP/DAHC as the matrix, but this was not so with CHCA. In DIOS, the signal from cysteine sulfonic acid-containing peptides was suppressed; however, the use of DAHC significantly enhanced the signal intensity with an increase in the number of observed peptides and increased signal-to-noise ratio in the DIOS spectra. The results show that DAHC in the matrix or on the DIOS chip decreases discrimination and suppression effects in addition to suppressing alkali-adduct ions, which leads to a beneficial effect on protonation of peptides containing cysteine sulfonic acid.

Cysteine↗
PubMed1994

S-methyl N,N-diethylthiolcarbamate sulfone, an in vitro and in vivo inhibitor of rat liver mitochondrial low Km aldehyde dehydrogenase.

S-Methyl N,N-diethylthiolcarbamate sulfone (DETC-Me sulfone) was investigated for its rat liver mitochondrial low Km aldehyde dehydrogenase (ALDH2) inhibitory properties. DETC-Me sulfone inhibited ALDH2 in vitro (IC50 = 3.8 microM) and in vivo (ID50 = 170 mumol/kg; 31 mg/kg). Maximum inhibition (60%) of ALDH2 was observed 8 hr after DETC-Me sulfone administration. In addition, incubation of S-methyl N,N-diethylthiolcarbamate (DETC-Me) or S-methyl N,N-diethylthiolcarbamate sulfoxide (DETC-Me sulfoxide) with rat liver microsomes and an NADPH-generating system failed to produce DETC-Me sulfone. Furthermore, DETC-Me sulfone could not be detected in plasma from rats treated with either DETC-Me sulfoxide or DETC-Me sulfone. In conclusion, DETC-Me sulfone inhibited ALDH2 in vitro and in vivo. However, there was no evidence suggesting that DETC-Me sulfoxide was metabolized to DETC-Me sulfone.

Aldehyde Dehydrogenase↗
PubMed2005

Cadmium ion sorption onto lignocellulosic biosorbent modified by sulfonation: the origin of sorption capacity improvement.

Juniper (Juniperus monosperma), a small-diameter underutilized material, has been studied as a lignocellulosic biosorbent for removing heavy metals from water. In this study, juniper wood was modified by sulfonation to enhance sorption capacity for cadmium in water. The origin of the enhancement was investigated by observing the sorption behaviors and the change in surface functional group concentrations. Cadmium sorption by all juniper wood biosorbents studied was fast and the sorption capacity decreased with decreasing pH, similar to results found for other biosorbents. Sulfonated juniper was found to have at least twice the sorption capacity for cadmium removal from water compared to that of untreated juniper, though the sorption capacity increased with increasing pH. A slight increase in carboxylate content after sulfonation was likely responsible for a small portion of the enhancement. Elemental analysis showed an increase in sulfur content after sulfonation. Diffuse reflectance infrared Fourier transform (DRIFT) spectra showed a decrease in the band at 1660 cm(-1) in the range of carbonyl groups as a result of sulfonation. This indicates that coniferaldehyde groups in the lignin of juniper wood corresponding to this band were substituted into sulfonic acid groups after sulfonation. This interpretation was supported by both the color forming reaction with phloroglucinol-hydrochloric acid and the reaction mechanisms from the acid sulfite pulping process. Consequently, the enhancement of cadmium sorption capacity of juniper wood by sulfonation mainly originated from the production of sulfonic acid groups, which are binding sites for heavy metals.

Acrolein↗
PubMed2004

Beneficial effects of GW274150 treatment on the development of experimental colitis induced by dinitrobenzene sulfonic acid.

Inflammatory bowel disease is associated with inducible nitric oxide synthase (iNOS) expression, oxidative and nitrosative stress, and leukocyte infiltration in the colon. Here, we investigate the effects of the selective iNOS-inhibitor (S)-2-amino-(1-iminoethylamino)-5-thiopentanoic acid (GW274150) on the development of experimental colitis induced by dinitrobenzene sulfonic acid. When compared to dinitrobenzene sulfonic acid-treated mice, GW274150 (5 mg/kg i.p.)-treated mice subjected to dinitrobenzene sulfonic ACID-induced colitis experienced a significantly lower rate of the extent and severity of the histological signs of colon injury. Dinitrobenzene sulfonic acid-treated mice experienced hemorrhagic diarrhoea and weight loss. At 4 days after the administration of dinitrobenzene sulfonic acid, the mucosa of the colon exhibited large areas of necrosis. Immunohistochemistry for nitrotyrosine and poly (ADP-ribose) (PAR) showed an intense staining in the inflamed colon. Treatment of dinitrobenzene sulfonic acid-treated mice with GW274150 significantly reduced the degree of hemorrhagic diarrhoea and weight loss caused by administration of dinitrobenzene sulfonic acid. GW274150 also caused a substantial reduction of (i) the degree of colon injury, (ii) the rise in myeloperoxidase (MPO) activity (mucosa), (iii) the increase in staining (immunohistochemistry) for nitrotyrosine, as well as (iv) PARP activation caused by dinitrobenzene sulfonic acid in the colon. Thus, GW274150 treatment reduced the degree of colitis caused by dinitrobenzene sulfonic acid. We propose that selective inhibition of iNOS activity with GW274150 may be useful in the treatment of inflammatory bowel disease.

Animals↗
PubMed2005

3,5-bis(trifluoromethyl)phenyl sulfones in the direct Julia-Kocienski olefination.

3,5-bis(trifluoromethyl)phenyl (BTFP) sulfones 7 have been employed in the Julia-Kocienski olefination reaction with carbonyl compounds. Sulfones 7 are readily prepared in high yields (64-97%) from commercially available 3,5-bis(trifluoromethyl)thiophenol through an alkylation/oxidation two-step sequence. The stability of metalated BTFP sulfones has been studied and compared with heteroaryl benzothiazol-2-yl (BT), 1-phenyl-1H-tetrazol-5-yl (PT), and 1-tert-butyl-1H-tetrazol-5-yl (TBT) sulfones 9-11 under different reaction conditions. The Julia-Kocienski olefination between alkyl BTFP sulfones 7 and a wide variety of aldehydes affords the corresponding 1,2-disubstituted alkenes and dienes in good yields and stereoselectivities. This one-pot protocol can be performed using KOH at room temperature or the phosphazene bases P2-Et and P4-t-Bu at -78 degrees C or rt and has been successfully used in a high-yielding and stereoselective synthesis of various methoxylated stilbenes such as trimethylated resveratrol. These new reaction conditions for the Julia-Kocienski olefination reaction have been also studied with BT, PT, and TBT sulfones, giving poorer results. Methylenation of aliphatic and aromatic aldehydes, ketones, and 1,2-dicarbonyl compounds is carried out through the modified Julia olefination using BTFP methyl sulfone 7d to give terminal alkenes and dienes. Mechanistic studies of the olefination reaction between benzyl BTFP sulfone 7a and aromatic aldehydes performed by KOH-induced Smiles rearrangement of stereodefined syn- and anti-beta-hydroxyalkyl BTFP sulfones indicate that the stereocontrol of the reaction is determined in the elimination step.

Journal Article↗
PubMedDate not supplied

Dermal irritation assessment of three benzene sulfonate compounds.

Three benzene sulfonate compounds, benzene sulfonate, benzene meta-disulfonate, and para-phenol sulfonate, were reported to be present in groundwater sampled from residential wells near a former disposal site. Concentrations ranged from < 0.005 mg/L to 474 mg/L. Acute dermal irritation studies were performed on rabbits for each of the three sulfonate compounds to determine if they had the potential to cause irritation to the skin of persons using this groundwater for bathing, showering, or other uses where skin would be exposed. The studies were performed by Toxikon Corporation (Bedford, MA) in accordance with the United States Environmental Protection Agency (USEPA)'s 1998 Health Effects Test Guidelines. At the highest concentration tested (5000 mg/L), all three sulfonate compounds were considered to be slight irritants, producing very slight to mild erythema (Draize Score 1). In all cases, the reactions were reversible. At 2000 mg/L, benzene meta-disulfonate and para-phenol sulfonate caused no irritation and were considered not to be irritants. At 2000 mg/L, only benzene sulfonate was considered to be a slight irritant, producing a mild erythema that was completely reversible within 24 hours. Benzene sulfonate was not considered an irritant at 1000 mg/L or at 500 mg/L. It is important to note that all three sulfonate compounds produced only a slight irritation at the highest concentration tested. None of the compounds produced a moderate to severe irritation response (i.e., severe erythema, edema). Furthermore, any irritation response observed at the highest concentrations tested was reversible within 72 hours. The only irritation response observed at the second highest dose was also reversible within 24 hours.

Administration, Topical↗