Discovery of isoerianin analogues as promising anticancer agents |
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Authors: | Messaoudi Samir Hamze Abdallah Provot Olivier Tréguier Bret Rodrigo De Losada Jordi Bignon Jérôme Liu Jian-Miao Wdzieczak-Bakala Joanna Thoret Sylviane Dubois Joëlle Brion Jean-Daniel Alami Mouad |
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Affiliation: | Université Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, 5 Rue J.-B. Clément, Chatenay-Malabry, 92296, France. |
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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 G2/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. |
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Keywords: | antitumor agents combretastatins erianin isoerianin tubulin |
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