Comparative study on the bioactivation mechanisms and cytotoxicity of Te-phenyl-L-tellurocysteine, Se-phenyl-L-selenocysteine, and S-phenyl-L-cysteine

摘要: Tellurium compounds are effective antioxidants and chemoprotectors, even more active than their selenium sulfur analogues. In addition to these properties, some compounds, such as selenocysteine Se-conjugates, possess significant chemopreventive antitumor activities, selenol metabolites considered species. the present study, we have synthesized Te-phenyl-L-tellurocysteine evaluated its bioactivation cytotoxicity. The activities of this compound were compared with those corresponding Te-Phenyl-L-tellurocysteine is bioactivated into tellurol, detected by GC-MS, cysteine conjugate beta-lyase amino acid oxidase, analogously what has been shown previously for Se-phenyl-L-selenocysteine. rate beta-elimination may reflect bond strength C-S, C-Se, C-Te bond. Bioactivation analogues oxidative enzymes was measuring NADPH-dependent activation hepatic mGST inhibition EROD. Se-phenyl-L-selenocysteine displayed strong time-dependent activation, while S-phenyl-L-cysteine resulted in no activation. also a inhibitor EROD activity. inhibition, strongest several human cytochrome P450 isoenzymes followed Se-phenyl-L-selenocysteine, weakest inhibitor. Interestingly, selectively inhibited 1A1 directly, which is, example, responsible procarcinogens. Preliminary cytotoxicity studies freshly isolated rat hepatocytes showed depletion GSH LDH leakage comparable relatively nontoxic drug paracetamol, toward hepatocytes. conclusion, because thought be mediated via tellurium might tellurocysteine Te-conjugates an interesting novel class prodrugs formation biologically tellurols.