Novel A-ring and B-ring modified combretastatin A-4 (CA-4) analogues endowed with interesting cytotoxic activity

  • J Med Chem. 2008 Oct 9;51(19):6211-5. doi: 10.1021/jm8005004.
Daniele Simoni  1 ,  Romeo Romagnoli ,  Riccardo Baruchello ,  Riccardo Rondanin ,  Giuseppina Grisolia ,  Marco Eleopra ,  Michele Rizzi ,  Manlio Tolomeo ,  Giuseppe Giannini ,  Domenico Alloatti ,  Massimo Castorina ,  Marcella Marcellini ,  Claudio Pisano
Affiliations
  • 1. Dipartimento di Scienze Farmaceutiche, Università di Ferrara, Ferrara, Italy. [email protected]
PMID: 18783207 DOI: 10.1021/jm8005004
Abstract

A novel class of combretastatins, modified at A-ring or both A- and B-rings, mainly by replacement with benzofuran or benzo[b]thiophene, were synthesized. The new heterocombretastatins showed good cytotoxic activity on BMEC and H-460 cell lines. The aminocombretastatin 9f potently inhibits cell growth of BMEC and combretastatin-resistant HT-29 cell lines, with potential interest to treat colon carcinoma. Heterocombretastatins 9a,b inhibit tubulin polymerization similarly to CA-4 by having a binding to colchicine site five times stronger.