Objective:To detect the antifungal effect of the novel imidazoles 2-imidazole-2, 4-pentadienone 19 and 44 onCandida albicans, and explore the mechanism of the antifungal effect preliminarily.Methods:The inhibitory effects of 2-imidazole-2, 4-pentadienone 19 and 44 onCandida albicansstandard strains SC5314, ATCC90028 and clinical isolates were observed through susceptibility testin 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 inCandida albicanswere 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 testin vitroshowed that the minimal inhibitory concentrations (MIC) of fluconazole, new drug 19, and new drug 44 onCandida albicansSC5314 were 1.00, 0.50, and 2.00 μg/mL, respectively. The clinical isolates ofCandida albicans21897, 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 ofCandida albicansSC5314 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 onCandida albicansby changing the structure of cell membrane.