SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives

Title:SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives

Volume: 19 Issue: 35

Author(s): J. Liu, K.-L. He, X. Li, R.-J. Li, C.-L. Liu, W. Zhong and S. Li

Affiliation:

Keywords: Cardiomyocytes protection, UPR, endoplasmic reticulum (ER) stress, eukaryotic translation initiation factor 2 subunit α (eIF2α) phosphorylation, PP1/GADD34 complex inhibitor, salubrinal, structure–activity relationships (SAR), MTT, CoMFA model, predicted abilities.

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).

Cite this article as:

Liu J., He K.-L., Li X., Li R.-J., Liu C.-L., Zhong W. and Li S., SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives, Current Medicinal Chemistry 2012; 19 (35) . https://dx.doi.org/10.2174/0929867311209066072