Dihydro-1,4-benzothiazine-6,7-dione, the ultimate toxic metabolite of 4-S-Cysteaminylphenol and 4-S-Cysteaminylcatechol

Hasegawa, Kiyokazu; Ito, Shosuke; Inoue, Shigeki; Wakamatsu, Kazumasa; Ozeki, Hiroyuki; Ishiguro, Isao

doi:10.1016/s0006-2952(97)00075-0

Cited by 43 publications

(26 citation statements)

References 20 publications

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“…4-S-CAP is metabolized by tyrosinase to 4-S-cysteaminylcatechol, which auto-oxidates to the ultimate toxin dihydro-1,4-benzothiazine-6,7-dione ( Fig. 11) (Pankovich et al, 1990;Hasegawa et al, 1997). N-Ac-4-S-CAP was shown to induce tyrosinase-dependent apoptosis, but also nontyrosinase-mediated cytostatic cytotoxicity (Thomas et al, 1999).…”

Section: Enzyme-catalyzed Activation Of Prodrugsmentioning

confidence: 99%

Enzyme-Catalyzed Activation of Anticancer Prodrugs

2004

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Section: Enzyme-catalyzed Activation Of Prodrugsmentioning

confidence: 99%

Enzyme-Catalyzed Activation of Anticancer Prodrugs

2004

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“…These agents are metabolized by tyrosinase to give rise to highly cytotoxic radicals and quinones. Quinones are capable of reacting rapidly with crucial SH groups and forming thiol adducts, for example with GSH and DNA polymerase α, thereby exerting a cytotoxic effect towards the melanocytes [29, 46, 47, 48]. The production of quinones capable of binding to intracellular thiols or other critical macromolecules serves as the cornerstone of the melanocytotoxic ability of chemicals.…”

Section: Depigmenting and Melanocytotoxic Agentsmentioning

confidence: 99%

Peroxidase-Mediated Mechanisms Are Involved in the Melanocytotoxic and Melanogenesis-Inhibiting Effects of Chemical Agents

Kasraee¹

2002

Dermatology

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Melanogenesis is based on the enzymatic conversion of the amino acid tyrosine, through a series of intermediates, to melanin pigments. The nature of the enzymes involved in the different steps of melanogenesis has been intensely debated. However, it is now believed that tyrosinase is responsible for the conversion of tyrosine to dopa and of dopa to dopaquinone, and that peroxidase accomplishes the oxidative polymerization of the eventually formed indoles to eumelanin pigments. Some very few investigators have also considered a main role for peroxidase in initiating melanogenesis. At present, most different hypotheses are focused on tyrosinase-mediated mechanisms to elucidate the melanocytotoxic and depigmenting activities of chemicals. However, many properties of these agents cannot be explained by such mechanisms. Most of the melanocytotoxic agents (e.g. hydroquinone, catechols, butylated hydroxyanisole) can be converted to cytotoxic species, such as quinones, by the peroxidase-H₂O₂ system. On the other hand, many of the melanogenesis inhibitors which are not known to inhibit tyrosinase (e.g. glucocorticoids, ascorbic acid, indomethacin) have the capacity to strongly inhibit peroxidase activity. We have proposed that peroxidase-mediated mechanisms, in addition to or in several instances rather than tyrosinase-mediated mechanisms, can explain the melanocytotoxic and depigmenting properties of such agents.

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“…on days 29 and 43, one week before and after the rechallenge by B16F1 transplantation, respectively. cysteine residues, resulting in melanoma-specific cytotoxicity [23][24][25].…”

Section: Discussionmentioning

confidence: 99%