Antifungal activity of styrylpyridinium compounds against Candida albicans

We synthesized a set of 13 new and earlier described styrylpyridinium compounds (N-alkyl styrylpyridinium salts with bromide or tosylate anions) in order to evaluate antifungal activity against C. albicans cells, to assay the possible synergism with fluconazole, and to estimate cytotoxicity to mammalian cells. All compounds were synthesized according to a well-known two-step procedure involving alkylation of γ-picoline with appropriate alkyl bromide and further condensation with substituted benzaldehyde. Compounds with long N-alkyl chains (C₁₈ H₃₇ -C₂₀ H₄₁ ) had no antifungal activity against the cells of all tested C. albicans strains. Other styrylpyridinium compounds were able to inhibit yeast growth at the concentrations of 0.06-16 μg/ml. At fungicidal concentrations, the compound with the CN- group was least toxic to mammalian cells, showed the most effective synergism with fluconazole, and only slightly inhibited the respiration of C. albicans. The compound with the 4'-diethylamino group exhibited the strongest fungicidal properties and effectively blocked the respiration of C. albicans cells. However, toxicity to mammalian cells was also high. Summarizing, the results of our study indicate that styrylpyridinium compounds are promising candidates in the development of new antifungal drugs.