erianin and Neoplasms

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.

Topics: Antineoplastic Agents; Bibenzyls; Binding Sites; Cell Division; Cell Line, Tumor; Computer Simulation; Crystallography, X-Ray; Drug Evaluation, Preclinical; Drug Screening Assays, Antitumor; G2 Phase; Humans; Molecular Conformation; Neoplasms; Phenol; Tubulin; Tubulin Modulators