Portal de Periódicos da CAPES

Discovery of Isoerianin Analogues as Promising Anticancer Agents

2011; Wiley; Volume: 6; Issue: 3 Linguagem: Inglês

10.1002/cmdc.201000456

1860-7187

Samir Messaoudi, Abdallah Hamzé, Olivier Provot, Bret Tréguier, Jordi Rodrigo de losada, Jérôme Bignon, Jianmiao Liu, Joanna Wdzieczak‐Bakala, Sylviane Thoret, Joëlle Dubois, Jean‐Daniel Brion, Mouâd Alami,

Phytochemistry and Biological Activities

Abstract The cytotoxic activity of a series of 23 new isoerianin derivatives with modifications on both the A and B rings was studied. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. The most cytotoxic compound, isoerianin ( 3 ), strongly inhibits tubulin polymerization in the micromolar range. Moreover, isoerianin leads to G 2 /M phase cell‐cycle arrest in H1299 and K562 cancer cells, and strongly induces apoptosis. Isoerianin also disrupts the vessel‐like structures formed by human umbilical vein endothelial cells (HUVECs) in vitro, suggesting that this compound may act as a vascular disrupting agent. It clearly appears that in this compound series, the 1,1‐ethane bridge encountered in isoerianin derivatives can replace the 1,2‐ethane bridge of natural erianin with no loss of activity. This reinforces the bioisosteric replacement approach in the combretastatin series previously reported by our research group.