Design, synthesis, molecular modeling, and biological evaluation of novel α-aminophosphonates based quinazolinone moiety as potential anticancer agents: DFT, NBO and vibrational studies

Diphenyl (aryl) (4-oxo-2-phenyl-4H-quinazolin-3-yl)-acetic acid hydrazino methyl phosphonate (IIIa-k) was achieved upon the reaction of 3, 4-dihydro-(4-oxo-2-phenyl-4H-quinazolin-3-yl)-acetic acid hydrazide I with various aromatic aldehydes (IIa-k), triphenylphosphite in the presence of anhydrous zinc chloride as a Lewis acid catalyst. The structure of the synthesized compounds was elucidated by FT-IR, H-1 NMR,C-13 NMR, P-31 NMR, elemental analysis and MS spectral data. The newly synthesized compounds were screened in vitro for their anticancer activities against four representative cell lines of HePG-2, MCF-7, HCT-116, and PC-3, and antioxidant activities. The results showed clearly that most of the synthesized alpha-aminophosphonates displayed an excellent to a moderate anti-proliferative activity against the four tested cell lines. Compounds IIIb and IIIk are the most potent antioxidant and anticancer agents. DFT calculations with B3LYP/6-31 + G (d) level were used to analyze the electronic and geometric characteristics deduced from the stable structure of the compounds. Theoretical FT-IR of all investigated compounds was studied to show a correlation between the theoretical wave numbers and the experimental ones. The principal quantum chemical descriptors showed a good correlation with the anticancer activity. (C) 2018 Elsevier B.V. All rights reserved.