Discovery and synthesis of novel luteolin derivatives as DAT agonists

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• 作者：Jiange Zhang ; Xianbo Liu ; Xinsheng Lei ; Lei Wang ; Lihe Guo ; Gang Zhao ; Guoqiang Lin
• 关键词：Luteolin ; Dopamine transporter ; Agonist ; Synthesize
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2010
• 出版时间：15 November 2010
• 年：2010
• 卷：18
• 期：22
• 页码：7842-7848
• 全文大小：351 K

文摘

Luteolin, 5,7-dihydroxy-2-(3,4-dihydroxyphenyl)-4H-chromen-4-one, has been proposed and proved to be a novel dopamine transporter (DAT) activator. In order to develop this potential of luteolin, a series of novel luteolin derivatives were designed, synthesized, and evaluated for their DAT agonistic activities, utilizing constructed Chinese hamster ovary (CHO) cell lines stably expressing rat DAT. Biological screening results demonstrated that luteolin derivatives 1d, 1e, and 4c carry great DAT agonistic potency (EC₅₀ = 0.046, 0.869, and 1.375 μM, respectively) compared with luteolin 8 (EC₅₀ = 1.45 ± 0.29 μM). Luteolin derivative 1d, notably, exhibited a 32-fold-higher DAT agonistic potency than luteolin. These luteolin derivatives represent a novel DAT agonist class, from which lead compounds useful for exploration of additional novel DAT agonists could be drawn.