2. Academic Validation
  3. Synthesis and cytotoxic activity of new 9-substituted camptothecins

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

Affiliation

  • 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.

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