Abstract:

Objective: To detect the antifungal effect of the novel imidazoles 2-imidazole-2, 4-pentadienone 19 and 44 on Candida albicans, and explore the mechanism of the antifungal effect preliminarily. Methods: The inhibitory effects of 2-imidazole-2, 4-pentadienone 19 and 44 on Candida albicans standard strains SC5314, ATCC90028 and clinical isolates were observed through susceptibility test in vitro (the concentration gradients of fluconazole, 2-imidazole-2, 4-pentadienone 19 and 44 were all set in 0.25-128.00 μg/mL), hyphal inhibition test (the concentration gradients of fluconazole, 2-imidazole-2, 4-pentadienone 19 and 44 were all set in 0, 2.00, 8.00, 16.00 μg/mL) and crystal violet staining cell coun-ting test (the concentration gradients of fluconazole, 2-imidazole-2, 4-pentadienone 19 and 44 were all set 2.00, 8.00, 16.00, 64.00 μg/mL). The morphological changes of membrane and organelles in Candida albicans were observed by transmission electron microscopy when they were cultured with 2-imidazole-2, 4-pentadienone 19 (0.50 μg/mL) and 44 (2.00 μg/mL). Results: The susceptibility test in vitro showed that the minimal inhibitory concentrations (MIC) of fluconazole, new drug 19, and new drug 44 on Candida albicans SC5314 were 1.00, 0.50, and 2.00 μg/mL, respectively. The clinical isolates of Candida albicans 21897, 210 and 141 were all fluconazole-resistant strains (MIC>128.00 μg/mL). The MICs of new drug 19 on three type isolates were 64.00 μg/mL,> 128.00 μg/mL and 64.00 μg/mL, and the MICs of new drug 44 on them were 8.00 μg/mL, 16.00 μg/mL and 16.00 μg/mL, respectively. The mycelial inhibition experiment showed that the mycelial growth of Candida albicans SC5314 was significantly inhibited in the culture medium containing fluconazole and the novel drugs 19 and 44, and the higher the drug concentration (≤64.00 μg/mL). The inhibitory effects of new drugs 19 and 44 were better than fluconazole as the drug concentrations were 8.00 μg/ml or 64.00 μg/mL. Transmission electron microscopy showed that fluconazole and the novel drugs 19 and 44 led the cell membrane of SC5314 to become uneven and coarse in texture, which was obviously different from that of drug-free control. Conclusions: The new imidazoles 2-imidazole-2, 4-pentadienone 19 and 44 show strong inhibitory effects on Candida albicans by changing the structure of cell membrane.

Key words: Candidaalbicans, New imidazole drugs, Inhibition, Cell membrane