Indole derivatives as potent inhibitors of 5-lipoxygenase: Design, synthesis, biological evaluation, and molecular modeling

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• 作者：Mingfang Zheng ; Mingyue Zheng ; Deju Ye ; Yangmei Deng ; Shuifeng Qiu ; Xiaomin Luo ; Kaixian Chen ; Hong Liu ; Hualiang Jiang
• 关键词：Indole derivatives ; 5-Lipoxygenase ; Inhibitor ; Molecular modeling
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2007
• 出版时间：1 May 2007
• 年：2007
• 卷：17
• 期：9
• 页码：2414-2420
• 全文大小：393 K

文摘

A series of novel indole derivatives was designed, synthesized and evaluated by cell-based assays for their inhibitory activities against 5-LOX in rat peritoneal leukocytes. Most of them (30 out of 35) showed an inhibitory potency higher than the initial screening hit 1a (IC₅₀ = 74 μM). Selected compounds for concentration–response studies showed prominent inhibitory activities with IC₅₀ values ranging from 0.74 μM to 3.17 μM. Four compounds (1m, 1s, 4a, and 6a) exhibited the most potent inhibitory activity compared to that of the reference drug (Zileuton), with IC₅₀ values less than 1 μM. Molecular modeling studies for compounds 1a, 3a, 4a, and 6a were also presented. The excellent in vitro activities of this class of compounds may possess potential for the treatment of LT-related diseases.