Design, synthesis, and cytoprotective effect of 2-aminothiazole analogues as potent poly(ADP-ribose) polymerase-1 inhibitors

Journal of Medicinal Chemistry
Wen-Ting ZhangJian-Guo Chen

Abstract

A series of novel poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors were designed within 2-aminothiazole analogues (4-10) based on a constructed three-dimensional pharmacophore model. After synthesis, the inhibitory effect on PARP-1 activity and the cytoprotective action of these compounds were tested and evaluated. Among them, compounds 4-6 and 10 appeared to be potent PARP-1 inhibitors with IC(50) values less than 1 microM, which had been perfectly predicted by pharmacophore model. These compounds proved to be highly potent against cell injury induced by H(2)O(2) and oxygen-glucose deprivation (OGD) in PC12 cells. These novel 2-aminothiazole analogues are potentially applicable as neuroprotective agents for the treatment of neurological diseases.

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Citations

Nov 10, 2011·Journal of Molecular Modeling·Alexey A ZeifmanGhermes G Chilov
Jan 31, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Wen-Yu WuJin-Ao Duan
May 3, 2011·Chemical & Pharmaceutical Bulletin·Mohammad Sayed AlamDong-Ung Lee
Dec 3, 2014·Chemical & Pharmaceutical Bulletin·Mohammad Sayed AlamDong-Ung Lee
Oct 15, 2019·Chemistry & Biodiversity·Chiyu SunXiaofeng Chen
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed Farouk ElsadekMohamed Fawzi Farahat

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