Inhibition of Cyclin Dependent Kinase-2 and Glycogen Synthase Kinase-3 by Herbal Derivative 1, 2-disubstituted Idopyranose through In-silico Analysis

Cyclin dependant kinase-2 (CDK-2) is a key regulator of cell cycle progression and glycogen synthase kinase-3 (GSK3) that plays a critical role in the regulatory pathway of serine/threonine kinase, which is being targeted for the treatment of human cancer. The natural product of 1, 2 disubstituted idopyranose (C23H28O12) was isolated from the leaves of the medicinal plant, Vitex negundo to treat human cancer. The bioactive compound of functionalized 1, 2 disubstituted idopyranose was studied through molecular docking and evaluated for their inhibitory activity against CDK2 and GSK3 using GLIDE module and also ADME/T properties of the analog was analyzed using QikProp module. Based on the docking studies, we have identified some key features in the 1, 2 disubstituted idopyranose that is responsible for simulations of a promising lead compound for the inhibition of CDK-2 and GSK-3 inhibitory activity. The 1, 2 disubstituted idopyranose, which showed docked energy -33.82 kcal/mol demonstrated against CDK-2 (2c4g) and docked energy -55.94 kcal/mol demonstrated against GSK-3 (3f7z). A series of 1, 2 disubstituted idopyranose demonstrated good inhibition against CDK-2 and GSK-3 and are useful candidates as leads for the development of potential anticarcinogenic agents.