title: Discovery of isoerianin analogues as promising anticancer agents.
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.
authors.affiliation: Université Paris-Sud, CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Faculté de Pharmacie, 5 Rue J.-B. Clément, Châtenay-Malabry, 92296, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Messaoudi
authors.forename: Abdallah
authors.initials: A
authors.lastname: Hamze
authors.forename: Olivier
authors.initials: O
authors.lastname: Provot
authors.forename: Bret
authors.initials: B
authors.lastname: Tréguier
authors.forename: Jordi
authors.initials: J
authors.lastname: Rodrigo De Losada
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bignon
authors.forename: Jian-Miao
authors.initials: JM
authors.lastname: Liu
authors.forename: Joanna
authors.initials: J
authors.lastname: Wdzieczak-Bakala
authors.forename: Sylviane
authors.initials: S
authors.lastname: Thoret
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Brion
authors.forename: Mouad
authors.initials: M
authors.lastname: Alami
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D001632:Bibenzyls / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D001665:Binding Sites; D002455:Cell Division; D045744:Cell Line, Tumor; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase; D006801:Humans; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy; D019800:Phenol; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001632:Bibenzyls; C477638:Erianin; D014404:Tubulin; D050257:Tubulin Modulators; D019800:Phenol