Synthesis and evaluation of indole-containing 3,5-diarylisoxazoles as potential pro-apoptotic antitumour agents

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• 作者：Siti Farah Md Tohid^a ; Noha I. Ziedan^a ; Fabio Stefanelli^b ; Stefano Fogli^b ; ^{stefano.fogli@farm.unipi.it} ; Andrew D. Westwell^a ;
• 关键词：3 ; 5-Disubstituted isoxazoles ; Indoles ; Pro-apoptotic antitumour agents ; Anticancer activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：October, 2012
• 年：2012
• 卷：56
• 期：Complete
• 页码：263-270
• 全文大小：493 K

文摘

A series of novel indole-containing diarylisoxazoles has been synthesised, based on our previous work on the synthesis and pro-apoptotic antitumour activity of indole-based diaryl 1,2,4-oxadiazoles. Concise synthetic routes to both 3-(indol-2-yl)-5-phenylisoxazoles and 5-(indol-2-yl)-3-phenylisoxazoles have been developed with full regiochemical control, bearing substituents on the indole ring, indole nitrogen, and/or phenyl group. Additionally a series of the related 5-(1H-indol-5-yl)-3-phenylisoxazoles has been prepared. In?vitro evaluation in human cancer cell lines Colo320 (colon) and Calu-3 (lung) revealed preferential antiproliferative activity within the 5-(indol-5-yl)-3-phenylisoxazole series (low micromolar IC₅₀). Further analysis revealed the ability of the indol-5-yl series to induce expression of effector caspases-3 and -7, and retention of viability of the human bronchial smooth muscle cell (BSMC) control cell population (particularly for compounds 18c and 18e).