Synthesis and cytotoxic activity of new 9-substituted camptothecins

A series of novel 9-substituted camptothecins derived from 9-formylcamptothecin were synthesized. The aldehyde was obtained from 10-hydroxycamptothecin or, better, by total synthesis. The compds. showed antiproliferative activity higher than that of the ref. compd. topotecan. Modeling suggested the possibility of a favorable interaction of small and polar 9-substituents with the topoisomerase I-DNA complex, which is consistent with the higher activity of these derivs. with respect to the corresponding 7-substituted camptothecins