Synthesis, docking, MD simulation, ADMET, drug likeness, and DFT studies of novel furo[2,3-b]indol-3a-ol as promising Cyclin-dependent kinase 2 inhibitors

A new series of furo[2,3-b]indol-3a-ol derivatives was synthesized to investigate their potential as inhibitors of the Cyclin-dependent kinase 2 (CDK2) Enzyme. CDK2 is a serine/threonine protein kinase belonging to a family of kinases involved in the control of the cell cycle. Based on results from clinical studies, it has been shown that overexpression of CDK2 may play a role in the development of Cancer. In order to discover highly effective derivatives, a process of in silico screening was carried out. The obtained results revealed that compound 3f. had excellent binding energies. In this study, in silico screening was used to investigate protein-ligand interactions and assess the stability of the most favorable conformation. The methods utilized included molecular docking, density functional theory (DFT) calculations using the B3LYP/6-31++G(d,p) basis set in the gas phase, molecular dynamic (MD) simulation, as well as the evaluation of drug-likeness scores. The pharmacokinetic and drug-likeness properties of the novel furo[2,3-b]indol-3a-ol derivatives suggest that these compounds have the potential to be considered viable candidates for future development as Anticancer drugs.