Design, synthesis, and characterization of guanidine derivative with broad-spectrum antimicrobial and antidiabetic inhibitory activities: a comprehensive spectroscopic and computational study.

AIMS: We synthesized and characterized a novel guanidine derivative, 2-(guanidino(2-hydroxyphenyl)methyl)hydrazine carbothioamide (GHC), and examined its antimicrobial and antidiabetic potential using spectroscopic, in-vitro, and in-silico approaches.

MATERIALS AND

METHODS

GHC was characterized by Fourier transform infrared spectroscopy (FTIR) and 1H- and 13C-NMR (nuclear magnetic resonance). Antimicrobial activity was evaluated by disc diffusion against Escherichia coli, Staphylococcus aureus, Aspergillus flavus, and Candida albicans. α-Amylase inhibition was determined by enzyme assays, and docking, quantum mechanics-molecular mechanics (QM/MM), and density functional theory (DFT) calculations were used to elucidate binding to α-amylase.

RESULTS

GHC produced inhibition zones of 17 mm (E. coli), 16 mm (S. aureus), 18 mm (A. flavus), and 16 mm (C. albicans), comparable to amoxicillin standards. It inhibited α-amylase with an IC50 of 81.70 µg/mL (acarbose: 20.41 µg/mL). Computational analyses supported stable complexation (binding energy -65.16 kcal/mol) and favorable residue-level contacts. absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions indicated high aqueous solubility (Log S -2.8), low acute toxicity (predicted LD50 > 2000 mg/kg), and overall drug-like properties.

CONCLUSIONS

GHC shows broad-spectrum antimicrobial activity and measurable α-amylase inhibition, warranting further optimization to improve efficacy and pharmacokinetics.