Design, Synthesis, Computational Studies and Evaluation of Novel Hybrid Bipyrimidine Analogues for Anticancer Activity against MCF-7 and A549 Cell Lines

A series of novel hybrid bipyrimidine derivatives were designed, synthesized and evaluated for their anticancer activity against the breast cancer cell line MCF-7 and the lung cancer cell line A549. The structures of all the synthesized molecules were confirmed using various spectroscopic techniques. Molecular docking studies were conducted using Maestro software from Schrödinger, targeting the crystal structure of the ErbB4 kinase (PDB ID: 3BBT). Lapatinib and gefitinib were used as reference drugs to compare binding affinities with the ErbB family of receptor tyrosine kinases. Several of the synthesized bipyrimidine derivatives demonstrated promising activity, with [Formula: see text] values comparable to the standard drug doxorubicin and gefitinib. Notably, compound PP-10 exhibited equipotent effects when compared to the reference drugs in both breast and lung cancer cell lines. Additionally, compounds PP-07 and PP-09 showed significant potency against the MCF-7 cell line, while compounds PP-02, PP-09, PP-11 and PP-14 were active against the A549 cell line. These novel hybrid bipyrimidine derivatives served as potential lead molecules in the development of novel drug-like molecules for the treatment of breast and lung cancer.