Synthesis and cytotoxic activity of a new series of topoisomerase I inhibitors

  • Bioorg Med Chem Lett. 2008 Feb 15;18(4):1484-9. doi: 10.1016/j.bmcl.2007.12.055.
Sabrina Dallavalle  1 ,  Sonia Gattinoni ,  Stefania Mazzini ,  Leonardo Scaglioni ,  Lucio Merlini ,  Stella Tinelli ,  Giovanni L Beretta ,  Franco Zunino
Affiliations
  • 1. Dipartimento di Scienze Molecolari Agroalimentari, Università di Milano, via Celoria 2, 20133 Milano, Italy.
PMID: 18248813 DOI: 10.1016/j.bmcl.2007.12.055
Abstract

A series of structurally simple analogues of natural topopyrone C were synthesized and tested for cytotoxic and Topoisomerase I inhibitory activities. The removal of the hydroxyl groups at the 5 and 9 positions resulted in an increased cytotoxic potency and ability to stabilize topoisomerase-mediated cleavage. In addition, the results suggest that some structural features, such as the pyrone ring and a polar group in position 11, are fundamental for Topoisomerase I inhibitory effect. These structural requirements are also consistent with the cytotoxic activity.