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Aim and Objective: Synthesis of new .-aminophosphonates containing quinazoline moiety through Kabachnik-Fields reaction in the presence of copper triflate catalyst [32], followed by studying their antimicrobial activities and in vitro anticancer activities against liver carcinoma cell line (HepG2) with the hope that new anticancer agents could be developed. Also, the quantum chemical calculations are performed using density functional theory (DFT) to study the effect of the changes of molecular and electronic structures on the biological activity of the investigated compounds. Materials and Method: The structures of the synthesized compounds are confirmed by FT-IR, 1H NMR, 13C NMR, 31P NMR and MS spectral data. The synthesized compounds show significant antimicrobial and also remarkable cytotoxicity anticancer activities against liver carcinoma cell line (HepG2). Density functional theory (DFT) was performed to study the effect of the molecular and electronic structure changes on the biological activity. Results: It was found that the electronic structure of the substituents affects on the reaction yield. The electron withdrawing substituent, NO2 group 3b, on the aromatic aldehydes gave a good yield more than the electron donating substituent, OH group 3c. The electron deficient on the carbon atom of the aldehydic group may increase the interaction of the Lewis acid (Cu(OTf)2) and the Lewis base (imine nitrogen), and accordingly, facilitate the formation of imine easily, which is attacked by the nucleophilic phosphite species to give the α- aminophosphonates. Conclusion: The newly synthesized compounds exhibit a remarkable inhibition of the growth of Grampositive, Gram-negative bacteria and fungi at low concentrations. The cytotoxicity of the synthesized compounds showed a significant cytotoxicity against the liver cancer cell line (HepG 2). Also, it was shown from the quantum chemical calculations that the electron-withdrawing substituent increases the biological activity of the α-aminophosphonates more than the electron donating group which was in a good agreement with the experimental results. Also, a good agreement between the experimental FT-IR and the calculated one was found.

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 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.

Bioisosteres of amino acids called α-aminophosphonates have a variety of therapeutic properties. A set of procedures involving amine, aldehydes and triethylphosphite have been utilized to synthesize these compounds in presence of Lewis acid catalysts such as lithium perchlorate via the Kabachnik-Fields reaction. The diazonium salt of different aromatic amines affords new α-aminophosphonate azo dyes, IIIa-f in high yields. The structure of the newly synthesized compounds was elucidated by FT-IR, 1 HNMR, 13 C-NMR and elemental analysis. The anti-inflammatory and antioxidant of the newly dyes was also examined. Most of the synthesized α-aminophosphonate compounds displayed an excellent to moderate activity against COX-1 and COX-2. To demonstrate the relationship between the theoretical and the experimental characteristics, DFT/6-311G + + (d, p) calculations were performed to investigate the electrical and geometric properties derived from the stable structure of the compounds. The optimized dyes with printing paste conditions, were used to silk screen printing polyester, as well as their printing properties, light, washing, perspiration, rubbing, and sublimation fastness were tested. Meanwhile, the improved dyes demonstrated acceptable fastness results.