Functionalized 2-Amino-4H-1-Benzopyran-4-yl Phosphonate Scaffolds: Synthesis, Anticancer Evaluation and Computational Studies

Abstract

Prostate, breast, and lung cancers are various human cancers that have been associated with SRC kinase mutations. Therefore, the development of potent and selective SRC kinase inhibitors is an exciting area of interest for researchers. In this study, we synthesized a series of 2-amino-4H-1-benzopyran-4-yl phosphonate derivatives through a one-pot reaction involving appropriately substituted salicylaldehydes, malononitrile, and diethyl phosphite, with meglumine as the catalyst. We conducted in vitro screening of these compounds for their anticancer activity against human prostate cancer (DU-145), breast cancer (MCF-7), and lung cancer (A549) cell lines using the MTT assay. Notably, compounds 4a, 4j, 4k, and 4l exhibited promising anticancer activity. Molecular docking studies of these compounds supported their potential as therapeutic agents for SRC kinase inhibition. Specifically, compounds 4a, 4b, 4c, 4d, and 4e demonstrated strong ΔG binding affinities ranging from −7.9 to −7.4 kcal/mol. These findings suggest that these molecules hold promise for cancer treatment.