title: Design, synthesis, biological evaluation, and structure-activity relationships of substituted phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates as new tubulin inhibitors mimicking combretastatin A-4.
abstract: Sixty-one phenyl 4-(2-oxoimidazolidin-1-yl)benzenesulfonates (PIB-SOs) and 13 of their tetrahydro-2-oxopyrimidin-1(2H)-yl analogues (PPB-SOs) were prepared and biologically evaluated. The antiproliferative activities of PIB-SOs on 16 cancer cell lines are in the nanomolar range and unaffected in cancer cells resistant to colchicine, paclitaxel, and vinblastine or overexpressing the P-glycoprotein. None of the PPB-SOs exhibit significant antiproliferative activity. PIB-SOs block the cell cycle progression in the G(2)/M phase and bind to the colchicine-binding site on β-tubulin leading to cytoskeleton disruption and cell death. Chick chorioallantoic membrane tumor assays show that compounds 36, 44, and 45 efficiently block angiogenesis and tumor growth at least at similar levels as combretastatin A-4 (CA-4) and exhibit low to very low toxicity on the chick embryos. PIB-SOs were subjected to CoMFA and CoMSIA analyses to establish quantitative structure-activity relationships.
authors: Unité des Biotechnologies et de Bioingénierie, Centre de Recherche, CHUQ, Hôpital Saint-François d'Assise, Québec, Québec, Canada. sebastien.fortin.1@ulaval.ca
authors: Sébastien
authors: S
authors: Fortin
authors: Lianhu
authors: L
authors: Wei
authors: Emmanuel
authors: E
authors: Moreau
authors: Jacques
authors: J
authors: Lacroix
authors: Marie-France
authors: MF
authors: Côté
authors: Eric
authors: E
authors: Petitclerc
authors: Lakshmi P
authors: LP
authors: Kotra
authors: René
authors: R
authors: C-Gaudreault
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