IN SILICO STUDIES ON NEW INDAZOLE DERIVATIVES AS GSK-3Î² INHIBITORS
Objective: In silico studies were conducted on newly proposed Indazole derivatives as GSK-3Î² inhibitors to select the best possible drug candidates based on drug properties and bioactivity score of the compounds.
Methods: 31 Indazole derivatives and active GSK-3Î² Indazole inhibitor 3-(5-chloro-1-methyl-indol-3-yl)-4-[1-[3-(triazol-1-yl)propyl]indazol-3-yl]pyrrole-2,5-dione(IC50 of 0.003 Î¼M) were subjected to predict the mutagenic, tumorigenic, irritant, reproductive risks, and drug-relevant properties using OSIRIS Property Explorer. Further bioactivity scores were determined using Molinspiration online tools.
Results: The results of new GSK-3Î² inhibitors were compared with potent GSK-3Î² Indazole inhibitor to examine the prospective of the optimized compounds. The best possible drug candidates were reported after comprehensive analysis on predicted cLogP, solubility, molecular weight, topological molecular polar surface area (TPSA), drug- likeness, drug score properties and bioactivity score for different human targets like GPCR, ion channel, kinase, nuclear receptor, protease and enzymes.
Conclusion: Five compounds 282, 141, 161, 108 and 456 were reported as the best drug like candidates for GSK-3Î² regulation.