Insight Study For Repurposing Of Certain Anti‐Inflammatory Drugs Based On Aspirin and Salicylic Acid Scaffolds For The Treatment of Cancer as CDKs Inhibitors: Cheminformatics and Anticancer Studies

Abstract The highly increased and global mortality due to cancer has created an urgent need to discover promising targets for its treatment. Where drug repurposing was considered as an attractive approach that can facilitate the lead generation and optimization phases of drug discovery by repurposing existing agents to target diseases other than their primary uses. Cheminformatics studies represented in molecular docking as well as molecular dynamic simulation of salicylic acid / aspirin analogues and sulindac and indomethacin as anti‐inflammatory drugs were carried out to be used in drug repurposing as cyclin‐dependent kinases (CDKs) namely CDK2, CDK6, and CDK12 inhibitors. Sulindac displayed the best binding ligand to all the receptors. The CDKs inhibition effects of the three drugs namely sulindac, indomethacin and anthranilic acid demonstrated good inhibitory activity against CDK2, CDK6, and CDK12 ranging from 0.48 to 1.78 µM. Likewise, the cytotoxicity of the three drugs revealed potent anticancer effects ranging from 0.155 to 1.278 µM against three cancer cell lines: HCT‐116, MCF‐7, and HeLa cells. As a result, this repurposing technique saves a lot of time and money in order to discover new anticancer agents.