<i>In Silico</i> Screening for Novel Tyrosine Kinase Inhibitors with Oxindole Scaffold as Anti-Cancer Agents: Design, QSAR Analysis, Molecular Docking and ADMET Studies

Recently, anti-cancer targeting drugs are directed against specific molecules and signaling pathways. These agents have reasonable specificity, efficacy less side effects. Tyrosine kinases, which play an essential role in growth factor regulation, significant targets this type of therapy. Synthesized numerous tyrosine-kinase inhibitors (TKIs), such as substituted indolin-2-ones, effective anti-tumor anti-leukemia agents. In study, a series novel indolin-2-ones were studied kinase inhibitor analogs through quantitative structure–activity relationship (QSAR) analysis. Two chemometrics methods, multiple linear regression (MLR) partial least squares combined with genetic algorithm for variable selection (GA-PLS), employed to establish relationships between structural characteristics inhibitory activity used oxindole analogs. The GA-PLS was developed the best predictor validated QSAR model. data set compounds also by molecular docking investigate their binding mechanism active site tyrosine enzyme. According information obtained from models analysis, 40 new potent lead features introduced. Molecular docking, drug-likeness rules, ADMET bioavailability, toxicity prediction target identification carried out on newly designed oxindoles elucidate fundamental properties that affect activity.