Design, Synthesis, Analysis, Evaluation of Cytotoxicity Against MCF-7 Breast Cancer Cells, 3D QSAR Studies and EGFR, HER2 Inhibition Studies on Novel Biginelli 1,4-Dihydropyrimidines

Abstract

1,4-Dihydropyrimidines are usually synthesized from Biginelli reaction which are well known for their anti-cancer activity. A series of novel Biginelli-1,4-dihydropyrimidines are rationally designed, synthesized, purified, analyzed by IR, NMR, Mass spectrometry and screened against MCF-7 breast cancer cells for their anti-cancer activity by measuring the cytotoxicity. Dihydropyrimidines exhibited weak to significant cytotoxicity proportionate to their anti-cancer activity. 14, 7 and 5 have exhibited potent cytotoxicity amongst the screened 33 dihydropyrimidines. Most potent compound 14 is further tested for inhibition of EGFR (epidermal growth factor receptor) and HER2 (human epidermal growth factor receptor 2) expression at 2 different concentrations by taking lapatinib as standard in flow cytometry. 42.02% and 36.45% of cells expressing EGFR and HER2 were inhibited at 500nM/L concentration. Furthermore, 3D-QSAR studies were executed to elucidate structure activity relationships in a 3D grid space by plotting experimental vs predicted cytotoxic activities.