title: SAR, cardiac myocytes protection activity and 3D-QSAR studies of salubrinal and its potent derivatives.
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).
authors.affiliation: Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: K-L
authors.initials: KL
authors.lastname: He
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: R-J
authors.initials: RJ
authors.lastname: Li
authors.forename: C-L
authors.initials: CL
authors.lastname: Liu
authors.forename: W
authors.initials: W
authors.lastname: Zhong
authors.forename: S
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D002934:Cinnamates; D013844:Thiazoles; D013890:Thiourea; D019892:eIF-2 Kinase; C581549:N-(2,2,2-trichloro-1-(4-(4-chlorophenyl)thiazol-2-ylamino)ethyl)cinnamamide; C496827:salubrinal