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Synthesis and cytotoxic activity of new 9-substituted camptothecins |
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| Authors: | Dallavalle Sabrina Rocchetta Daniela Granza Musso Loana Merlini Lucio Morini Gabriella Penco Sergio Tinelli Stella Beretta Giovanni Luca Zunino Franco |
| Affiliation: | aDipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy bUniversità di Scienze Gastronomiche, Pollenzo, Italy cUnità di Chemioterapia e Farmacologia Antitumorale Preclinica, Dipartimento di Oncologia Sperimentale e Laboratori, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy |
| 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 compounds showed antiproliferative activity higher than that of the reference compound topotecan. Modelling suggested the possibility of a favourable interaction of small and polar 9-substituents with the topoisomerase I–DNA complex, which is consistent with the higher activity of these derivatives with respect to the corresponding 7-substituted camptothecins. |
| Keywords: | Camptothecin Antitumor agents Topoisomerase I DNA cleavage Synthesis |
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