Ultrasonic-assisted synthesis of novel α-Aminophosphonates via Kabachnik-fields reaction: In Silico insights, molecular docking, DFT, MDS, and antimicrobial evaluation

Abstract

• The novel α-aminophosphonates were synthesized using ultrasound environmentally friendly, green chemistry approach pathways. • Molecular docking and molecular dynamics simulations studies were performed to evaluate the binding interactions of the synthesized compounds with microbial and fungal targets their stability and binding affinity in a dynamic biological environment. • Density Functional Theory (DFT) calculations were employed to analyze the electronic properties of the compounds and the Structures of compounds were verified using ¹H, ³¹P, ¹³C NMR, and IR spectroscopy. • Exhibited Strong activity against on K. pneumoniae (33 mm) and Candida sp . • Potential design framework for tyrosyl-tRNA inhibitors. A one-pot green synthetic approach has been devised for the creation of novel aminophosphonates through a three-component Kabachnik-Fields reaction involving 2-aminoalcohol, triethylphosphite, and benzaldehyde under ultrasound irradiation. Using this established method, we successfully synthesized four organophosphorus derivatives with high yields. The target compounds were characterized by 1 H, 31 P, 13 C NMR and IR. Molecular docking was carried out against tyrosyl-tRNA synthetase; the AutoDock results indicated that the investigated compounds can fit within the binding pocket of Tyrosyl-tRNA synthetase. The in vitro antimicrobial potential of synthesized compounds was screened against eight species, Staphylococcus aureus and Streptococcus sp. as a Gram-positive bacterium. Moreover, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii as Gram-negative bacteria, and two fungal strains, Candida albicans and Candida sp .