SEARCHING OF NEW ANTIMICROBIAL AGENTS FROM SYNTHETIC COMPOUNDS

Abstract

Background: The rapid emergence of antimicrobial resistance (AMR) has substantially reduced the effectiveness of conventional antimicrobial agents, creating an urgent need for the development of novel therapeutic compounds. Synthetic molecules with diverse chemical scaffolds represent promising candidates for combating multidrug-resistant (MDR) bacterial and fungal pathogens.

Objective: This study aimed to evaluate the in vitro antibacterial and antifungal activities of newly synthesized naphthalene-imidazole, salicylic acid, oxime, and zuclopenthixol derivatives against a broad spectrum of clinically important microorganisms.

Materials and Methods: A total of 42 synthetic compounds were screened against Gram-positive bacteria, Gram-negative bacteria, and fungal isolates using the Kirby–Bauer disc diffusion method. Compounds exhibiting significant antimicrobial activity (zone of inhibition ≥15 mm) were further evaluated by broth microdilution assay to determine the minimum inhibitory concentration (MIC). Agar well diffusion was also performed to compare the antimicrobial activity with the disc diffusion method.

Results: Among the evaluated compounds, naphthalene-imidazole derivatives demonstrated promising antibacterial activity against Bacillus cereus, Enterobacter aerogenes, and Shigella dysenteriae, while selected derivatives also exhibited moderate antifungal activity against Candida albicans, Saccharomyces cerevisiae, Trichophyton rubrum, and Fusarium spp. Salicylic acid derivatives showed only weak antibacterial activity and no detectable antifungal activity. Oxime derivatives exhibited moderate antibacterial activity against selected bacterial species, whereas only one oxime derivative (SN-26-241012) demonstrated moderate antifungal activity. Zuclopenthixol derivatives showed the broadest antibacterial spectrum, producing strong inhibitory activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). MIC values for the most active compounds ranged from 6.25 to 25 µg/mL. The disc diffusion and agar well diffusion methods produced comparable antimicrobial results, although disc diffusion provided greater consistency.

Conclusion: The findings demonstrate that naphthalene-imidazole and zuclopenthixol derivatives possess significant antimicrobial potential and may serve as promising lead molecules for the development of new antimicrobial agents. Further investigations, including toxicity evaluation, mechanism-of-action studies, structure–activity relationship analysis, and in vivo validation, are warranted to support their therapeutic development.