QSAR studies of novel potent benzamide derivatives as glucokinase activators

• Published in: Medicinal chemistry research 2013-09, Vol.22 (9), p.4331-4337
• Main Authors: Jain, Nimisha, Mundada, Anand B., Pathak, Anupam K.
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Original Research; Pharmacology/Toxicology
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-012-0435-x

Two-dimensional QSAR studies of benzamide derivatives as allosteric glucokinase activators agents were performed on a series of 47 compounds. The structures were sketched using chemsketch 12.5 versions then subjected to energy minimization, and the lowest energy structures were used to calculate the physiochemical properties using Vlife MDS 3.5 version for molecular modeling study. The best model so generated from QSAR studies showed regression values having n  = 32, r 2  = 0.8669, q 2  = 0.6423, pred_ r 2  = 0.6408, r 2 se = 0.3247, q 2 se = 0.3650, pred_ r 2 se = 0.3635 (standard errors), and descriptor so generated were chiV4pathcluster, SsNH2E-index, and SdssCE-index. The study revealed that increase in the activity was due to bulky substitution on benzamide and thiazole moiety. Moreover, –NH 2 group plays a significant role in activating glucokinase enzyme by binding specifically on the position of benzamide. This binding will lead to formation of hydrogen bond between tyrosine present in enzyme and amino group of concerned benzamide moiety. This study can help in rational drug design and synthesis of new allosteric glucokinase activator with predetermined affinity.