Discovery of novel anticancer candidates based on a combination strategy of synthesis, characterization, biological activity evaluation, consensus docking and molecular modeling

Through the Kabachnic-Fields three-component reaction of 3(2-amino-acetyl)-quinazolin-4(3H)-one, compound III, various aromatic aldehydes, triphenyl phosphite, and lithium perchlorate as Lewis acid catalyst, new a-amino phosphonates molecules, IVa-f have been produced in a high yield. FT-IR, H-1-NMR, elemental analysis, and mass spectral data were used to determine the structures of the newly synthesized chemicals. Examined phosphonates, Iva-f, have been tested for their in vitro anticancer effects on the five cell lines HePG-2, MCF-7, Hela, HCT-116, PC-3, and normal cell, WI-38. Newly synthesized compounds' antioxidant activities were also covered. The novel-created a-amino phosphonate compounds have been evaluated on six cell lines and exhibit good anti-proliferative properties. The IVc molecule is the most effective antioxidant and anticancer candidate. Utilizing DFT/B3LYP/6-311G (d, p) method, the electronic and geometric characteristics derived from the stable structure of the studied compounds were examined. Additionally, there are outcomes for HOMO-LUMO, molecule electrostatic potential, and quantum chemical parameters. The stability of the most active phosphonate molecule, IVc, is attributed to hyper-conjugative interactions and charge delocalization. This was investigated using NBO analysis. Theoretical FT-IR and H-1-NMR measurements were applied to demonstrate the relationship between theory and experiment. An excellent concurrence between experimental and theoretical data was discovered. A docking simulation study was applied to forecast the inhibitory mode of action of the most active substance inside the cavity of estrogen receptor-positive (ER +) MCF-7 breast cancer.