α-Aminophosphonates: Antimicrobial, Anti-Inflammatory, Antioxidant Activities, Molecular Docking, and DFT Studies

Three alpha-aminophosphonates derived from 2-hydroxybenzaldehyde were synthesized and evaluated their biological activities. The antimicrobial and antibiofilm properties of compounds 1A, 1B, and 1C were evaluated against a range of pathogenic bacteria and fungi, including four Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens; one Gram-positive bacterium: Staphylococcus aureus; and five yeasts of the Candida genus: Candida albicans, Candida kefyr, Candida krusei, Candida lusitaniae, and Candida tropicalis. The antioxidant activity of these compounds was assessed by DPPH (2,2-diphenyl-1-picrylhydrazyl). Determination of the anti-inflammatory activity of the compounds in vitro was carried out using bovine serum albumin (BSA) protein. Computational analysis was carried out using density functional theory (DFT) with the B3LYP 6-31G (d,p) basis set, and the theoretical results were correlated with experimental data. Molecular docking study was carried out to give insights into the interactions of three derivatives with the binding sites of thymidylate kinase (TMK) in S. aureus. Compound 1b uses its phenol group to create a hydrogen bond with the amino acid Gln101. Additionally, its phenyl ring engages in a pi-stacking interaction with Tyr100 and Phe66 in the hydrophobic zone of the S. aureus TMK binding site.