Comparative antimicrobial activity of metronidazole and it's metal complexes against anaerobic pathogens

Abstract

Background: Metronidazole is a widely utilized antimicrobial agent known for its efficacy against obligate anaerobic pathogens. However, its activity spectrum and potential limitations in the face of resistance have prompted exploration of structural modifications. Recent research has focused on synthesizing metal complexes of metronidazole with the aim of enhancing antimicrobial potency, improving pharmacological properties, and overcoming emerging resistance. Methods: A series of metronidazole complexes were synthesized with vanadium (IV), chromium (III), iron (III), manganese (II), cobalt (II), copper (II), zinc (II), palladium (II), platinum (II), and gold (III) ions. Characterization employed elemental analysis, UV-Vis and IR spectroscopy, ESR, magnetic susceptibility, and thermal studies to confirm structure and composition. Antimicrobial activity was evaluated against clinical and standard strains of Bacteroides fragilis, Bacteroides melaninogenicus, Clostridium tetani, and Clostridium welchii via disc diffusion and broth dilution (MIC) methods. Broader susceptibility screening included additional Gram-negative and Gram-positive bacteria, assessing both metal ions alone and in combination with ciprofloxacin. Results: Most metronidazole-metal complexes retained or enhanced the activity of the parent drug, especially vanadium, manganese, cobalt, and zinc complexes, which exhibited strong inhibition zones and favorable MIC values. Complexes with chromium, iron, and gold showed moderate but still clinically meaningful activity. All Clostridium species tested were highly susceptible to both metronidazole and its metal complexes. Dose-dependent activity and a strong correlation between inhibition zone diameter and MIC values were observed. The combination of metals with ciprofloxacin produced synergistic effects against several bacterial species. Conclusion: Metal complexation of metronidazole generates promising antimicrobial agents with enhanced or retained activity profiles. These findings support further research and development of metronidazole-metal complexes as potential therapies for anaerobic and resistant bacterial infections.