Synthesis and cytotoxic activity of new 9-substituted camptothecins

  • Bioorg Med Chem Lett. 2008 May 1;18(9):2781-7. doi: 10.1016/j.bmcl.2008.04.016.
Sabrina Dallavalle  1 ,  Daniela Granza Rocchetta ,  Loana Musso ,  Lucio Merlini ,  Gabriella Morini ,  Sergio Penco ,  Stella Tinelli ,  Giovanni Luca Beretta ,  Franco Zunino
Affiliations
  • 1. Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, Via Celoria 2, 20133 Milano, Italy. [email protected]
PMID: 18434153 DOI: 10.1016/j.bmcl.2008.04.016
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.