Main Article Content
Abstract
Background: Fungal infections represent a growing global health concern, particularly among immunocompromised populations. The emergence of resistance to existing antifungal agents highlights the urgent need for novel therapeutic compounds. Benzimidazole derivatives, owing to their structural versatility and broad pharmacological spectrum, have gained significant attention as promising antifungal leads.
Objectives: To rationally design, synthesize, and characterize a series of novel 2-substituted benzimidazole derivatives (B1–B6) and to evaluate their in-vitro antifungal activity against Candida albicans, Aspergillus niger, and Aspergillus fumigatus in comparison with the standard drug Fluconazole.
Methods: Six novel benzimidazole derivatives were synthesized via condensation of o-phenylenediamine with substituted aromatic aldehydes under acidic catalytic conditions. Compounds were purified by recrystallization and characterized by melting point, Thin Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FT-IR), Proton Nuclear Magnetic Resonance Spectroscopy (¹H-NMR), and Mass Spectrometry (MS). In-vitro antifungal activity was assessed using the agar well diffusion method at 100 µg/mL, with inhibition zones measured in triplicate. Structure–Activity Relationships (SAR) were analyzed across the compound series.
Results: All six derivatives were obtained in satisfactory yields (68–78%) with narrow melting ranges indicative of purity. Spectroscopic analyses confirmed the benzimidazole scaffold and substituent identities. Antifungal screening revealed that compound B5 (2-(4-hydroxy-3-methoxyphenyl)-1H-benzimidazole) exhibited the highest activity across all three fungal strains, with mean inhibition zones of 18.0, 19.0, and 18.0 mm against C. albicans, A. niger, and A. fumigatus respectively. Compound B6 (2-(4-bromophenyl)-1H-benzimidazole) demon-strated the second-strongest activity. SAR analysis indicated a positive correlation between electron-withdrawing/lipophilic substituents and antifungal potency.
Conclusion: The synthesized benzimidazole derivatives demonstrate promising antifungal activity, with B5 and B6 emerging as the most active leads. Although activity was lower than Fluconazole, the compounds provide valuable lead structures amenable to further optimization. These findings support the benzimidazole scaffold as a productive framework for novel antifungal drug development.