In silico investigation of novel isatin derivatives as potential multi-target anticancer agents targeting VEGFR-2, EGFR, and caspase-6

Abstract

The isatin scaffold has emerged as a promising platform for the development of anticancer agents, as evidenced by several clinically relevant isatin-based compounds. In this study, 85 novel isatin derivatives were designed based on literature reports and evaluated using drug-likeness prediction, ADME profiling, molecular docking, and molecular dynamics simulations. The compounds were screened against VEGFR-2, EGFR, and caspase-6 to identify potential multi-target lead candidates. Based on their binding affinity and pharmacokinetic properties, 41 compounds were shortlisted for further evaluation. Among them, compound 4 exhibited the most favorable binding profile and stable interactions with the selected targets. These findings suggest that compound 4 represents a promising lead for further investigation. However, experimental studies, including enzyme inhibition, cell-based assays, and in vivo evaluation, are required to validate its therapeutic potential. Overall, this study highlights the usefulness of computational approaches in the discovery of novel isatin-based multi-target lead candidates for cancer therapy.