Investigating the Effectiveness of Spirocyclopropane-Oxindole Derivatives on Clinical Isolates of Candida albicans

Objectives: Given the spread of azole resistance in Candida albicans (C. albicans), searching for new potent compounds, such as spirocyclopropane-oxindole derivatives is important. This study evaluates the antifungal susceptibility of spirocyclopropane-oxindole derivatives on clinical isolates of C. albicans.  Methods: Antifungal susceptibility of 50 clinical isolates of C. albicans to spirocyclopropane-oxindole derivatives (4a, 4b, and 4c), nystatin, and fluconazole were evaluated according to Clinical Laboratory Standards Institute (M27-S4) guidelines. The medicinal dilution range of the compounds, fluconazole, and nystatin was 0.256 to 128, 0.128 to 64, and 0.032 to 16 μg/mL, respectively. The minimum inhibitory concentration (MIC) was defined as the concentration that caused at least 50% growth inhibition compared to the positive control. Statistical analysis was performed using the SPSS software, version 20. The significance level was set at P≤0.05. Results: There was a significant difference between the MIC values of spirocyclopropane-oxindole derivatives (4a, 4b, and 4c), nystatin, and fluconazole against C. albicans. The comparison of the MICs of the spirocyclopropane-oxindole derivatives (4a, 4b, and 4c) against C. albicans showed that derivative 4a had a lower MIC50 (8 μg/mL), MIC90 (16 μg/mL), and Geometric (G) Mean (10.126) than derivatives 4b (MIC50=64, MIC90=128, G Mean=76.638), and 4c (MIC50=64, MIC90=128, G Mean=60.547). Discussion: Antifungal effects of spirocyclopropane-oxindole derivatives (4a, 4b, and 4c) on C. albicans isolates were significantly less than nystatin and fluconazole. Therefore, with structural changes, the antifungal effects of these compounds will increase.