Title:Synthesis of New α-Amino Phosphonates Containing 3-Amino-4(3H) Quinazolinone Moiety as Anticancer and Antimicrobial Agents: DFT, NBO, and Vibrational Studies
Volume: 15
Issue: 2
Author(s): Mohamed K. Awad*, Mahmoud F. Abdel-Aal, Faten M. Atlam and Hend A. Hekal
Affiliation:
- Chemistry Department, Faculty of Science, Tanta University, Tanta 31527,Egypt
Keywords:
Antimicrobial agents, Anticancer agents, Quinazolinone derivatives, -aminophosphonates, three-component Kabachnic-Fields
reaction, computational studies, natural bond orbital (NBO) analysis, vibrational studies.
Abstract: 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.
Material 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.
