Isatin Derivatives as Emerging Frontiers in Cancer Treatment: Recent Updates in Synthesis, Anticancer Effect, and SAR Studies

Abstract

Due to its extensive biological activity and structural heterogeneity, the special nitrogen‐containing heterocyclic compound isatin (1 H ‐indole‐2,3‐dione) has attracted significant interest. This paper explains the synthesis and action of heterocyclic isatin hybrids that induce apoptosis by blocking kinases, serving as an appropriate model for the development of new anticancer drugs. Isatin has significant potential to form potent isatin hybrids and conjugates that target multiple carcinogenic pathways through various chemical modifications. Remarkably, isatin hybrids have demonstrated anticancer activity across numerous cancer cell lines. Their activities include inhibition of tubulin polymerization, caspase activation, apoptosis mediated by mitochondria, and regulation of kinases. Several synthetic isatin‐based drugs show excellent IC 50 values and low toxicity against normal cells. This review also summarizes recent synthetic advancements like microwave‐assisted and multi‐component methods. In addition to summarizing recent advances, this review critically integrates SAR, molecular docking, kinase selectivity, synthetic feasibility, CADD, predictive ADMET profiling, and translational challenges to afford a complete roadmap for isatin‐based anticancer drug discovery. Overall, these findings reveal that isatin is a useful framework for developing new anticancer drugs. In the future, nano‐formulation drug delivery systems with new drug signaling pathways will be promoted to increase bioavailability and targeted delivery, especially in solid tumors.