The concise synthesis of chalcone, indanone and indenone analogues of combretastatin A4

被引:96
作者
Kerr, Daniel J.
Hamel, Ernest
Jung, M. Katherine
Flynn, Bernard L.
机构
[1] Monash Univ, Fac Pharm, Dept Med Chem, Parkville, Vic 3052, Australia
[2] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Ft Detrick, MD 21702 USA
[3] NCI, SAIC Frederick, NIH, Frederick, MD 21702 USA
关键词
tubulin polymerisation inhibitor; chalcone; indanone; indenone;
D O I
10.1016/j.bmc.2007.02.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A series of aryl- and aroyl-substituted chalcone analogues of the tubulin binding agent combretastatin A4 (1) were prepared, using a recently introduced one-pot palladium-mediated hydrostannylation-coupling reaction sequence. These chalcones were converted to indanones by Nazarov cyclisation, followed by oxidation to give the corresponding indenones. Indenones were also prepared using a palladium-mediated formal [3+2]-cycloaddition process between ortho-halobenzaldehydes and diarylpropynones. All compounds were assessed as inhibitors of tubulin polymerisation, but only E-31 had activity similar to that of 1. However, compound E-31 did not exhibit antiproliferative activity against the MCF-7 cell line. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3290 / 3298
页数:9
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