Synthesis, Characterization, and Biological Evaluations of Eugenol-Amide Hybrids as Promising Antimicrobial Agents:...

Eugenol-derived compounds have recently garnered significant attention in medicinal chemistry as a novel class of agents with potential as drug candidates for diverse therapeutic applications. This study aims to synthesize novel eugenol-amide hybrids and evaluate their antimicrobial response against various pathogenic fungal (Candida albicans ATCC 10231) and bacterial strains (Escherichia coli ATCC 25922, Pseudomonas aeruginosa CIP A22, Staphylococcus aureus ATCC 25923). The synthesized hybrids were thoroughly characterized using infrared spectroscopy, ¹H/¹³C nuclear magnetic resonance (NMR), and mass spectrometry. Results reveal that compounds 4c, 4k, and 4n exhibit moderate antibacterial activity, with minimum inhibitory concentration (MIC) values spanning 3.9-31.25 µg/mL. Compounds 4c and 4k showed the most potent antifungal activity against C. albicans (MIC value of 3.9 µg/mL), surpassing that of fluconazole (MIC value of 7.8 µg/mL), whereas derivatives 4e, 4f, 4i, and 4j exhibited significant antifungal effects (p < 0.05) comparable to fluconazole. In silico analysis indicates that most derivatives possess favorable predicted pharmacokinetic properties and low toxicity. Furthermore, molecular docking studies revealed enhanced binding free energy scores for the top compounds, whereas molecular dynamics simulations were performed to evaluate the stability of the resulting protein-ligand complexes.