Abstract
Various classes of cytotoxic compounds which alkylate cellular thiols are described namely α, β-unsaturated ketones, α-methylene-γ -lactones, azines of Mannich bases, imexon, isothiocyanates, a benzoacronycine as well as activation by thiols prior to alkylation. The mechanisms of action of some of the molecules, such as the formation of reactive oxygen species, are presented. The cytotoxicity of a number of drugs can be influenced by modulation of the concentration of thiols including the observation that potencies can be increased by thiol activation. The ability of certain thiol reagents to reverse multidrug resistance as well as some miscellaneous actions of thiol alkylators are described.
Keywords: Thiols, alkylating agents, α,β-unsaturated ketones, αmethylene-γ-lactones, azines, imexon, isothiocyanates, benzoacronycine, tumour sensitization, drug resistance
Mini-Reviews in Medicinal Chemistry
Title: Cytotoxic Thiol Alkylators
Volume: 7 Issue: 2
Author(s): Hari N. Pati, Umashankar Das, Rajendra K. Sharma and Jonathan R. Dimmock
Affiliation:
Keywords: Thiols, alkylating agents, α,β-unsaturated ketones, αmethylene-γ-lactones, azines, imexon, isothiocyanates, benzoacronycine, tumour sensitization, drug resistance
Abstract: Various classes of cytotoxic compounds which alkylate cellular thiols are described namely α, β-unsaturated ketones, α-methylene-γ -lactones, azines of Mannich bases, imexon, isothiocyanates, a benzoacronycine as well as activation by thiols prior to alkylation. The mechanisms of action of some of the molecules, such as the formation of reactive oxygen species, are presented. The cytotoxicity of a number of drugs can be influenced by modulation of the concentration of thiols including the observation that potencies can be increased by thiol activation. The ability of certain thiol reagents to reverse multidrug resistance as well as some miscellaneous actions of thiol alkylators are described.
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Cite this article as:
Pati N. Hari, Das Umashankar, Sharma K. Rajendra and Dimmock R. Jonathan, Cytotoxic Thiol Alkylators, Mini-Reviews in Medicinal Chemistry 2007; 7 (2) . https://dx.doi.org/10.2174/138955707779802642
DOI https://dx.doi.org/10.2174/138955707779802642 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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