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  2. Discovery and synthesis of novel luteolin derivatives as DAT agonists

Discovery and synthesis of novel luteolin derivatives as DAT agonists

  • Bioorg Med Chem. 2010 Nov 15;18(22):7842-8. doi: 10.1016/j.bmc.2010.09.049.
Jiange Zhang 1 Xianbo Liu Xinsheng Lei Lei Wang Lihe Guo Gang Zhao Guoqiang Lin
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China. jgzhang5500@hotmail.com
Abstract

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 (EC(50)=0.046, 0.869, and 1.375μM, respectively) compared with luteolin 8 (EC(50)=1.45±0.29μM). 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.

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