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.
Synthesis and cytotoxic activity of new 9-substituted camptothecins / S. Dallavalle, D. Granza Rocchetta, L. Musso, L. Merlini, G. Morini, S. Penco, S. Tinelli, G.L. Beretta, F. Zunino. - In: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS. - ISSN 0960-894X. - 18:9(2008 May 01), pp. 2781-2787.
Synthesis and cytotoxic activity of new 9-substituted camptothecins
S. Dallavalle;D. Granza Rocchetta;L. Musso;L. Merlini;
2008
Abstract
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.
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