The chemistry of sulfenamides

Craine, Leslie E.; Raban, Morton

doi:10.1021/cr00094a001

Cited by 213 publications

(92 citation statements)

References 79 publications

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“…These experiments suggested attachment of GSH moiety to the amide nitrogen of flutamide via the N-S bond formation, thus forming a novel sulfenamide derivative. Sulfenamides are compounds containing trivalent nitrogen bonded to divalent sulfur (Craine and Raban, 1989). Several synthetic routes to sulfenamides have been developed over the years; however, information on the enzyme-catalyzed formation of these derivatives is relatively sparse.…”

Section: Discussionmentioning

confidence: 99%

“…However, several mechanisms that result in conjugation of GSH and flutamide can be speculated. Reports on the chemistry of sulfenamides have indicated that aromatic thiols can react with amines in the presence of oxygen and a metal catalyst to result in the corresponding sulfenamides, possibly via a radical mechanism (Craine and Raban, 1989). In addition, syntheses of sulfenamides from disulfides and amines have also been suggested.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Novel Glutathione Conjugate of Flutamide in Incubations with Human Liver Microsomes

Kang¹,

Dalvie²,

Smith³

et al. 2007

Drug Metab Dispos

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ABSTRACT:Flutamide, a nonsteroidal antiandrogen drug widely used in the treatment of prostate cancer, has been associated with rare incidences of hepatotoxicity in patients. It is believed that bioactivation of flutamide and subsequent covalent binding to cellular proteins is responsible for its toxicity. Current in vitro studies were undertaken to probe the cytochrome P450 (P450)-mediated bioactivation of flutamide and identify the possible reactive species using reduced glutathione (GSH) as a trapping agent. NADPH-and GSH-supplemented human liver microsomal incubations of flutamide gave rise to a novel GSH conjugate where GSH moiety was conjugated to the flutamide molecule via the amide nitrogen, resulting in a sulfenamide. The structure of the conjugate was characterized by liquid chromatography-tandem mass spectrometry and NMR experiments. The conjugate formation was primarily catalyzed by heterologously expressed CYP2C19, CYP1A2, and, to a lesser extent, CYP3A4 and CYP3A5. The mechanism for the formation of this conjugate is unknown; however, a tentative bioactivation mechanism involving a P450-catalyzed abstraction of hydrogen atom from the amide nitrogen of flutamide and the subsequent trapping of the nitrogen-centered radical by GSH or oxidized glutathione (GSSG) was proposed. Interestingly, the same adduct was formed when flutamide was incubated with human liver microsomes in the presence of GSSG and NADPH. This finding suggests that P450-mediated oxidation of flutamide via a nitrogen-centered free radical could be one of the several bioactivation pathways of flutamide. Even though the relationship of the GSH conjugate to flutamide-induced toxicity is unknown, the results have revealed the formation of a novel, hitherto unknown, GSH adduct of flutamide.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Glutathione Conjugate of Flutamide in Incubations with Human Liver Microsomes

Kang¹,

Dalvie²,

Smith³

et al. 2007

Drug Metab Dispos

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“…1). Literature reveals the availability of a variety of techniques for preparing both symmetric and unsymmertric disulfides, many of which are based upon the reaction of a thiol with a sulfenylating agent such as sulfenyl halides, 18) sulfenamides, 19) sulfinimides, 20) sulfenylhydrazides 21) and disulfides. 22) In the present case, sulfur monochloride in glacial acetic acid was proved to be excellent to synthesize the disulfide linkage as carbon of thiazole ring is very susceptible to S 2 Cl 2 thus avoiding the formation of the thiols first ( Table 2).…”

Section: ®1mentioning

confidence: 99%

Synthesis and Antibacterial Activity of Bis[2-amino-4-phenyl-5-thiazolyl] Disulfides

et al. 2007

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“…17,18 The reaction of sulfenyl chlorides with diarylamines is known to generate diarlyl sulfide B (Scheme 1) resulting from C-sulfenylation of the phenyl ring, but the electronic factors controlling the product distribution of A and B has not been fully understood. 19 For example, the diarylamines 1aÀ5a, 7a, and 14a gave N-sulfenylated products A exclusively, whereas 6a and 12a gave the C-sulfenylated isomers B exclusively. All other amines gave variable mixtures of A and B.…”

mentioning

confidence: 99%

Type 1 Phototherapeutic Agents, Part I: Preparation and Cancer Cell Viability Studies of Novel Photolabile Sulfenamides

Karwa

Poreddy

Asmelash

et al. 2011

ACS Med. Chem. Lett.

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Novel type 1 phototherapeutic agents based on compounds containing S–N bonds (sulfenamides) were synthesized, assessed for free radical generation, and evaluated in vitro for cell death efficacy in four cancer cell lines (U937, HTC11, KB, and HT29). All of the compounds were found to produce copious free radicals upon photoexcitation with UV-A and/or UV-B light, as determined by electron spin resonance spectroscopy. Among the sulfenamides, the most potent compounds were derived from dibenzazepine 7b and dihydroacridine 8b as determined in all of the four cancer cell lines.

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The chemistry of sulfenamides

Cited by 213 publications

References 79 publications

Identification of a Novel Glutathione Conjugate of Flutamide in Incubations with Human Liver Microsomes

Identification of a Novel Glutathione Conjugate of Flutamide in Incubations with Human Liver Microsomes

Synthesis and Antibacterial Activity of Bis[2-amino-4-phenyl-5-thiazolyl] Disulfides

Type 1 Phototherapeutic Agents, Part I: Preparation and Cancer Cell Viability Studies of Novel Photolabile Sulfenamides

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