Structural insights of oxindole based kinase inhibitors as anticancer agents: Recent advances

Small-molecule kinase inhibitors are being continuously explored as new anticancer therapeutics. Kinases are the phosphorylating enzymes which regulate numerous cellular functions such as proliferation, differentiation, migration, metabolism, and angiogenesis by activating several signalling pathways. Kinases have also been frequently found to be deregulated and overexpressed in cancerous tissues. Therefore, modulating the kinase activity by employing small molecules has emerged as a strategic approach for cancer treatment. On the other hand, oxindole motifs have surfaced as privileged scaffolds with significant multi-kinase inhibitory activity. The present review summarises recent advances in the development of oxindole based kinase inhibitors. The role of distinguished structural frameworks of oxindoles, such as 3-alkenyl oxindoles, spirooxindoles, 3-iminooxindoles and similar hydrazone derivatives have been described based on their kinase inhibition potential. Furthermore, the design strategies, mechanism of actions, structure activity relationships (SARs) and their mode of interaction with target protein have been critically highlighted. (C) 2021 Elsevier Masson SAS. All rights reserved.