SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives
Authors: Liu, J.; He, K.-L.; Li, X.; Li, R.-J.; Liu, C.-L.; Zhong, W.; Li, S.
Source: Current Medicinal Chemistry, Volume 19, Number 35, December 2012 , pp. 6072-6079(8)
Publisher: Bentham Science Publishers
Abstract:Salubrinal is a selective inhibitor of endoplasmic reticulum (ER) stress and affords remarkable protection to cardiomyocytes. By studying the structure–activity relationship (SAR) of salubrinal, it was found that modification of the quinoline ring terminus and thiourea unit could confer the compound PP1-24 with markedly enhanced cardioprotective activity (EC50 ≤ 0.3 μM) that is 50-fold more potent than salubrinal. Comparative molecular field analysis (CoMFA) was performed using the obtained biological data and resulted in a statistically significant CoMFA model with high predictive power (q2 = 0.741, r2 = 0.991).
Keywords: Cardiomyocytes protection; CoMFA model; MTT; PP1/GADD34 complex inhibitor; UPR; endoplasmic reticulum (ER) stress; eukaryotic translation initiation factor 2 subunit α (eIF2α) phosphorylation; predicted abilities; salubrinal; structure–activity relationships (SAR)
Document Type: Research Article
Publication date: 2012-12-01
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