Design, synthesis, in silico, and in vitro evaluation of novel pyrimidine phosphonates with cytotoxicity against breast cancer cells

Pyrimidine derivatives are widely used for the treatment of breast cancer and rapid efforts are contributing to develop highly potential novel molecules. In view of this, in this study, novel pyrimidine phosphonate molecules were designed so as to inhibit aromatase, a potential target of breast cancer. Quantitative structure activity relationship descriptors were defined and they revealed that the molecules have an effective and safer drug-like properties, which also supported by absorption, distribution, metabolism, and excretion study. Molecular docking of these compounds into the aromatase active site revealed that they are showing strong interaction forming H-bonds and arene cationic interactions. The ligand–receptor complex of compound 6i showed a best docking score of −15.776 kcal/mol among all. Hence, this compound was synthesized and tested in vitro at different concentrations of 25, 50, 100, and 200 μg/mL against MDA-MB-231 adenocarcinoma breast cancer cells and it exhibited excellent antiproliferative activity and also induced apoptosis. The results from in silico structure activity relationships, molecular docking study and in vitro assays suggesting the compound as a potential source of chemotherapeutic drug for the treatment and management of breast cancer.