Derivative of aminoresin as potent anti-virulence agent: Synthesis, spectral (FT-IR, UV, NMR) analysis, molecular docking, effect of polar solvation dynamics, and quantum chemical investigation

Abstract

This work undertakes a comprehensive study encompassing the synthesis, spectral characterization (FT-IR, UV, 1HNMR , 13CNMR), exploration of polar solvation dynamics (DMSO, EtOH, MeOH) on the molecular structure, quantum chemical calculations, topological (ELF, NCI) analysis, and molecular docking investigation. The focal point is a derivative of amino terpolymer resin, synthesized via the condensation of 4,4′-diaminodiphenylmethane, 8-hydroxyquinoline, and formaldehyde (DHQF). Thorough examination of the compound was conducted to evaluate its responsiveness in varying solvents and investigate its viability as a key candidate for antivirulent therapy against toxins from Vibrio cholerae and Salmonella enterica. Simulation of solvation dynamics underscored the compound's robust thermodynamic stability even at lower temperatures. Primary vibrations noted within the compound encompassed CH, OH, NH, CH2, and CN vibrations, whereas UV spectroscopy unveiled an electronic shift from HOMO to LUMO, featuring peak absorption at 292.77 nm, influenced by its interaction with DMSO. The molecular docking analysis reveals the terpolymer's significant bioactivity against proteins 7EE6 (affinity: −6.7 kcal/mol) and 5V6f (affinity: -7.1 kcal/mol) associated with V. cholerae and S. enterica. The binding affinity of DHQF with S. enterica toxin protein (PDB: 7EE6) is comparable to that of standard drug Ciprofloxacin (affinity: −6.9 kcal/mol) and the toxin protein. However, the binding affinity between DHQF and V. cholerae toxin protein 5V5F considerably surpasses the binding affinity (−4.6 kcal/mol) between Doxycycline and the toxin protein. More so, the complex shows close binding affinities to both proteins and a higher number of conventional hydrogen bonds, this formed multiple favorable interactions, particularly conventional hydrogen bonds, contributing significantly to the stability of the ligand-protein complexes. In conclusion, the analyzed terpolymer displayed favorable qualities and interactions, which establish it as a strong candidate for addressing the targeted V. cholerae and S. enterica pathogens. These findings highlight the compound's impressive stability and its potential for various therapeutic applications in different areas.