engleski

Quinuclidinium surfactants enhance drug activity against diverse fungal pathogens

The emergence of resistant fungal pathogens has been a motivating force in the search for new antifungal agents. Inspired by their diverse biological and pharmacological activity of quinuclidine and oxime compounds we have synthesized and characterized novel class of surfactants, 3-hydroxyimino quinuclidinium bromides with different alkyl chains lengths(CnQNOH ; n = 12, 14 and 16) to evaluated antifungal activity and their mechanism of action against eight Candida albicans including both azole-resistant and azole sensitive strains. The antifungal activities were established by determination of grow inhibition zones and MIC values by disk diffusion and broth microdilution assays and compared with fluconazole and itraconazole. The synergistic interaction between C12 and C14 with fluconazole and itraconazole was also evaluated against various strains of C. albicans using a microdilution checkerboard assay. To confirm the synergistic inhibitory effects of C12 or C14 and fluconazole against the azole-resistant C. albicans strains, representative kinetic time-kill studies were performed. Mechanism of action has been also determined by performing fluorescence study where a mixture of nucleic acid binding. Results demonstrated that investigated compounds showed broad-spectrum antifungal activities against azole-resistant and azole- sensitive C. albicans strains compared with fluconazole and itraconazole. Analogues with C12 and C14 chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 3.12 to 25.00 μg/mL and 0.78 to 6.25 μg/mL, respectively. However, analogue with C16 exhibited lower activity with MIC values ranging from 12.50 to 50 μg/mL. In addition, study demonstrated the synergistic combination effects between C12 or C14 and azoles against the majority of the C. albicans strains tested. The results obtained suggest the possible use of this surfactant as an alternative antifungal agent in the medical field for applications against C. albicans responsible for diseases and infections, making it a suitable alternative to conventional antifungal agent.

quinuclidinium surfactants ; antifungal activity ; Candida albicans

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