In Vitro Anticancer Activity, Molecular Docking and Structure–Activity Relationship (SAR) Studies of Some Phenylamino Derivatives

Abstract

We herein report the anticancer activity and molecular docking studies of a series of amide derivatives of two nonsteroidal anti-inflammatory drugs (mefenamic acid and ibuprofen). The hypothesis of drug repurposing has been successfully employed to explore the promising anticancer activity of analogs of known anti-inflammatory agents. The compounds have been tested for their inhibitory potential against cervical cancer cell lines by MTT assay using 5-fluorouracil as the reference standard. Among the compounds screened, 3aa [2-(2,3-dimethylamino)phenyl)(1H-indol-1-yl)methanone] and 3ad [2-(2,3-dimethylphenylamino)phenyl)(9H-carbazol-9-yl)methanone] displayed good potency of less than 25 µg/mL half-maximal inhibitory concentration (IC50). The docking analysis has confirmed that molecule 3aa effectively binds to the active site of the target protein CDK2, with a docking score of −9.21 Kcal/mol and a binding energy of −46.44 Kcal/mol, involving a hydrogen bond with Ile 10. The molecule 3ad also exhibited a good glide score of −6.78 Kcal/mol with the binding energy of −45.90 Kcal/mol. As many of the tested compounds displayed promising potency against cervical cancer cell lines, our investigation revealed the importance of drug repurposing in the development of lead molecules in medicinal chemistry.