M. Soussi, O. Provot, G. Bernadat
Aug 1, 2015
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0
Influential Citations
45
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Quality indicators
Journal
ChemMedChem
Abstract
A series of novel isocombretaquinazolines (isoCoQ) 4 were quickly prepared by coupling N‐toluenesulfonylhydrazones with 4‐chloroquinazolines under palladium catalysis. These compounds, which can be regarded as isocombretastatin A‐4 (isoCA‐4) analogues that lack the 3,4,5‐trimethoxyphenyl ring, displayed nanomolar‐level cytotoxicity against various human cancer cell lines and were observed to effectively inhibit tubulin polymerization. The isoCoQ compounds 2‐methoxy‐5‐(1‐(2‐methylquinazolin‐4‐yl)vinyl)phenol (4 b), 4‐[1‐(3‐fluoro‐4‐methoxyphenyl)vinyl]‐2‐methylquinazoline (4 c), and 2‐methoxy‐5‐(1‐(2‐methylquinazolin‐4‐yl)vinyl)aniline (4 d), which respectively bear the greatest resemblance to isoCA‐4, isoFCA‐4, and isoNH2CA‐4, are able to arrest HCT116 cancer cells in the G2/M cell‐cycle phase at very low concentrations. Preliminary in vitro antivascular assay results show that 4 d is able to disrupt a network of capillary‐like structures formed by human umbilical vein endothelial cells on Matrigel. All these results clearly demonstrate that replacement of the 3,4,5‐trimethoxyphenyl ring of isoCA‐4 with a quinazoline nucleus is a feasible approach toward new and highly promising derivatives with the potential for further development as antitubulin agents.