Phenylthio-derivatives of α-methylene-γ-lactones as pro-drugs of cytotoxic agents

被引:21
作者
Fardella, G [1 ]
Barbetti, P
Grandolini, G
Chiappini, I
Ambrogi, V
Scarcia, V
Candiani, AF
机构
[1] Univ Perugia, Inst Pharmaceut Chem & Technol, I-06100 Perugia, Italy
[2] Univ Trieste, Inst Pharmacol & Pharmacognosy, Trieste, Italy
关键词
sesquiterpene lactones; pro-drugs; cytotoxicity;
D O I
10.1016/S0223-5234(99)80100-7
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of substituted phenylthio-derivatives of grosheimin (1), a natural cytotoxic guaianolide, were investigated with the aim of providing insight into their mechanism of action as cytotoxic agents against KB cell lines. Hydrolysis data, kinetics, in the presence and in the absence of H2O2, and the valuation of lipophilicity were correlated with cytotoxicity values and with Hammett-sigma-values of substituents (R) at the thiophenol ring. These compounds behave as 'pro-drugs' which release the cytotoxic agent grosheimin by sulphur-oxidation promoted by H2O2 and subsequent retro-elimination which depends on the nature and position of the R substituent. (C) Elsevier, Paris.
引用
收藏
页码:515 / 523
页数:9
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