國家衛生研究院 NHRI:Item 3990099045/1254

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Title:	Concise synthesis and structure-activity relationships of combretastatin A-4 analogues, 1-aroylindoles and 3-aroylindoles, as novel classes of potent antitubulin agents
Authors:	Liou, JP;Chang, YL;Kuo, FM;Chang, CW;Tseng, HY;Wang, CC;Yang, YN;Chang, JY;Lee, SJ;Hsieh, HP
Contributors:	Division of Biotechnology and Pharmaceutical Research;National Institute of Cancer Research
Abstract:	The synthesis and study of the structure-activity relationships of two new classes of synthetic antitubulin compounds based on 1-aroylindole and 3-aroylindole skeletons are described. Lead compounds 3, 10, and 14 displayed potent cytotoxicities with IC50 = 0.9-26 nM against human NUGC3 stomach, MKN45 stomach, MESSA uterine, A549 lung, and MCF-7 breast carcinoma cell lines. The inhibition of proliferation correlated with in vitro polymerization inhibitory activities. Structure-activity relationships revealed that 6-methoxy substitution of 3-aroylindoles and 5-methoxy substitution of 1-aroylindoles contribute to a significant extent for maximal activity by mimicking the para substitution of the methoxy group to the carbonyl group in the case of aminobenzophenones. Addition of a methyl group at the C-2 position on the indole ring exerts an increased potency. The 3,4,5-trimethoxybenzoyl moiety was necessary for better activity but not essential and can be replaced by 3,5-dimethoxybenzoyl and 3,4,5-trimethoxybenzyl moieties. We conclude that 1- and 3-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.
Keywords:	Chemistry, Medicinal
Date:	2004-08-12
Relation:	Journal of Medicinal Chemistry. 2004 Aug;47(17):4247-4257.
Link to:	http://dx.doi.org/10.1021/jm049802l
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-2623&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000223142500019
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=3843136376
Appears in Collections:	[Hsing-Pang Hsieh] Periodical Articles [Shiow-Ju Lee] Periodical Articles [Jang-Yang Chang] Periodical Articles

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