Evaluation of 3, 3’-Disubstituted Oxindoles Derivatives as a Potential Anti- Cancer Tyrosine Kinase Inhibitors-Molecular Docking and ADME Studies

Abstract

This study aims to explore the binding interactions between synthesized 3,3’-Disubstituted Oxindoles and the HCK enzyme, with the specific goal of discovering potential anticancer agents. Cancer presents an ongoing global health challenge, necessitating the exploration of innovative therapeutic approaches. Isatin derivatives and pyridine compounds hold great promise for the development of anticancer drugs due to their wide-ranging biological activities. Moreover, HCK plays a significant role in chemotherapy resistance and reduced drug efficacy in clinical settings, highlighting its importance in the intricate network of cancer pathophysiology. There is an urgent need for targeted interventions to regulate HCK activity and enhance cancer treatment outcomes. In our study, we ensured meticulous optimization of protein and ligand preparation to guarantee accurate docking simulations. We conducted molecular docking analyses using the state-of-the-art Glide module and assessed ADME properties using the Schrödinger suite's QikProp tool. Through molecular docking, compounds 3c and 3e have emerged as promising anticancer agents with low docking scores against Tyrosine Kinase. Further ADME analysis has provided valuable insights into the compounds' in-silico behaviour, while computed dipole moments have enhanced our understanding of their physicochemical characteristics In this study, we explored how the synthesized compounds bind within the HCK active site, indicating potential anticancer properties. Through in silico docking, we identified compounds 3c and 3e as possible anticancer agents, with the lowest docking scores of -7.621 and -7.602 kcal/mol against Tyrosine Kinase. These findings emphasize the importance of computational approaches in drug discovery and offer valuable insights for future research and development efforts.