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

Abstract

AbstractThrough 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 α-amino phosphonates molecules, IVa-f have been produced in a high yield. FT-IR, 1H-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 α-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 1H-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.