Novel α‐Aminophosphonate Derivative: Antioxidant Activity, DFT Analysis, ADMET Profiling, and in Silico COVID‐19 Inhibition

Abstract

ABSTRACT A novel α‐aminophosphonate compound, diethyl (((2‐mercaptophenyl) amino) (4‐methoxyphenyl) methyl) phosphonate (DEMAMP), was synthesized via a reaction involving 2‐aminothiophenol, 4‐methoxybenzaldehyde, and triethyl phosphite. The chemical structure of DEMAMP was confirmed using various spectroscopic and physicochemical techniques, including FT‐IR, UV–Vis, NMR ( 1 H, 3 1 P), and melting point analysis. Density Functional Theory (DFT) calculations were performed to investigate the compoundʼs electronic properties, vibrational modes, and reactive sites, revealing promising electronic characteristics. The antioxidant activity of DEMAMP was assessed in vitro using DPPH radical scavenging, the phosphomolybdenum method, and H 2 O 2 scavenging assays, demonstrating significant antioxidant potential. ADMET profiling indicated favorable oral bioavailability. Computational modeling suggested that DEMAMP could serve as a potent inhibitor of NADPH oxidase, a key enzyme involved in oxidative stress, as well as two essential SARS‐CoV‐2 proteins: the main protease (Mpro) and RNA‐dependent RNA polymerase (RdRp). Molecular docking simulations indicated that DEMAMP effectively inhibits these targets, presenting a promising candidate for therapeutic applications against oxidative stress and viral infections like COVID‐19.