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 cytotoxicagents 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-σ-values of substituents (R) at the thiophenol ring. These compounds behave as `pro-drugs' which release the cytotoxicagent grosheimin by sulphur-oxidation promoted by H2O2 and subsequent retro-elimination which depends on the nature and position of the R substituent.
Phenylthio-Derivatives of a-Methylene-g-Lactones as Pro-Drugs of Cytotoxic Agents
FARDELLA, Giuseppe;GRANDOLINI, Giuliano;AMBROGI, Valeria;CHIAPPINI, Ione;BARBETTI, Paolo;
1999
Abstract
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 cytotoxicagents 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-σ-values of substituents (R) at the thiophenol ring. These compounds behave as `pro-drugs' which release the cytotoxicagent grosheimin by sulphur-oxidation promoted by H2O2 and subsequent retro-elimination which depends on the nature and position of the R substituent.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.