Antimicrobial activity of guanidine-based terpolymers: Synthesis, Spectroscopy (FT-IR, 1H, and 13C NMR), Quantum chemical investigation, and molecular docking

Abstract

This study presents a comprehensive assessment of the antimicrobial efficacy of a Guanidine-Based Terpolymer (DGF) utilizing a blend of experimental and theoretical methodologies. Structural insights were derived from experimental analyses, such as FT-IR, 1H, and 13C NMR data, along with mass spectra. Employing Density Functional Theory (DFT) at the DFT/B3LYP/aug-cc-pVDZ level of theory, accurate predictions of drug molecule properties including reactivity and stability were achieved. Results from the antimicrobial screening suggested that the studied compound has significant antimicrobial activity, with the highest effectiveness against Candida albicans (26 mm/ml), followed by Staphylococcus aureus (22 mm/ml), Aspergillus niger (22 mm/ml), and Escherichia coli (20 mm/ml). Substantially, from the pharmacokinetics, the studied compound against Staphylococcus aureus was evaluated, revealing favorable drug toxicity potentials with low values for Hepatotoxicity (P = 0.75), Carcinogenicity (P = 0.56), Immunotoxicity (P = 0.99), Mutagenicity (P = 0.56), and Cytotoxicity (P = 0.61), indicative of inactivity. Metabolism studies identified notable inhibitors, including CYP2C19 (++), CYP2C9 (+); CYP2D6 (++), and CYP3A4 (++). Additionally, molecular docking on fungal (C. albicans and A. niger) and bacterial (E. coli and S. aureus) proteins showcased robust binding affinities between the DGF ligand and the proteins tested against. Notably, DGF exhibited superior efficacy against C. albicans (-7.5 kcal/mol) compared to amphotericin B (-6.8 kcal/mol), while effectiveness against A. niger (-7.4 kcal/mol) was slightly lower than the standard drug (-9.6 kcal/mol). In bacterial investigations, DGF demonstrated heightened efficacy against S. aureus with a binding affinity of -8.1 kcal/mol and three conventional hydrogen bonds. Contrastingly, its standard drug, Penicillin, displayed a lower binding affinity (-7.4 kcal/mol) and formed three conventional hydrogen bonds. This analysis, consistent with prior antimicrobial studies, and proposes DGF as a potential antibacterial agent, especially against Gram-positive bacteria like Staphylococcus species, attributed to its presence of conventional hydrogen bonds and high binding affinity in interactions with S. aureus.