【摘 要】
：
Combretastatin A-4 (CA-4) is a natural product possessing effective anti-tubulin activity by binding at the colchicinebinding site oftubulin.Much effort has been invested in fixing the cis stereochemi
【机 构】
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Faculty of Pharmacy University Paris-Sud France
【出 处】
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(BITs 3rd Annual World Cancer Congress-2010, Breast Cancer C
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Combretastatin A-4 (CA-4) is a natural product possessing effective anti-tubulin activity by binding at the colchicinebinding site oftubulin.Much effort has been invested in fixing the cis stereochemistry in CA-4 by replacing its stilbene double bond with different heterocyclic ring systems.However, few studies were directed to modification of the linker length.Besides the synthesis of a large panel of derivatives (enynes, benzils, diarylmethanes...), we recently found that isoCA-4, the simplest isomer of the natural product was very promising.We use the 1, 1-diarylethylene scaffolds as a replacement for the Z-double bond in CA-4.A series of 1, 1-diarylethylene compounds with different substitution patterns at the 3-and 4-positions of the B-ring structure was synthesised.These compounds were evaluated for their antiproliferative activity against MCF-7 and MDA-MB-231 cell lines.A number of these showed activity in the low nanomolar range.A SAR of this series of compounds was carried out to provide a useful prediction for the design of further active ligands.
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