Structure-Activity Relationship Study and Design Strategies of Hydantoin, Thiazolidinedione, and Rhodanine-Based Kinase Inhibitors: A Two-Decade Review.

Cancer is one of the most prominent causes of the rapidly growing mortality numbers worldwide. Cancer originates from normal cells that have acquired the capability to alter their molecular, biochemical, and cellular traits. The alteration of cell signaling enzymes, such as kinases, can initiate and amplify cancer progression. As a curative method, the targeted therapy utilized small molecules' capability to inhibit kinase's cellular function. This review provides a brief history (1999-2023) of Small Molecule Kinase Inhibitors (SMKIs) discovery with their molecular perspective. Furthermore, this current review also addresses the application and the development of hydantoin, thiazolidinedione, and rhodanine-based derivatives as kinase inhibitors toward several subclasses (EGFR, PI3K, VEGFR, Pim, c-Met, CDK, IGFR, and ERK) accompanied by their structure-activity relationship study and their molecular interactions. The present work summarizes and compiles all the important structural information essential for developing hydantoin, thiazolidinedione, and rhodanine-based kinase inhibitors to improve their potency in the future.