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 ۵۰ clinical isolates of C. albicans to spirocyclopropane-oxindole derivatives (۴a, ۴b, and ۴c), nystatin, and fluconazole were evaluated according to Clinical Laboratory Standards Institute (M۲۷-S۴) guidelines. The medicinal dilution range of the compounds, fluconazole, and nystatin was ۰.۲۵۶ to ۱۲۸, ۰.۱۲۸ to ۶۴, and ۰.۰۳۲ to ۱۶ μg/mL, respectively. The minimum inhibitory concentration (MIC) was defined as the concentration that caused at least ۵۰% growth inhibition compared to the positive control. Statistical analysis was performed using the SPSS software, version ۲۰. The significance level was set at P≤۰.۰۵. Results: There was a significant difference between the MIC values of spirocyclopropane-oxindole derivatives (۴a, ۴b, and ۴c), nystatin, and fluconazole against C. albicans. The comparison of the MICs of the spirocyclopropane-oxindole derivatives (۴a, ۴b, and ۴c) against C. albicans showed that derivative ۴a had a lower MIC۵۰ (۸ μg/mL), MIC۹۰ (۱۶ μg/mL), and Geometric (G) Mean (۱۰.۱۲۶) than derivatives ۴b (MIC۵۰=۶۴, MIC۹۰=۱۲۸, G Mean=۷۶.۶۳۸), and ۴c (MIC۵۰=۶۴, MIC۹۰=۱۲۸, G Mean=۶۰.۵۴۷). Discussion: Antifungal effects of spirocyclopropane-oxindole derivatives (۴a, ۴b, and ۴c) on C. albicans isolates were significantly less than nystatin and fluconazole. Therefore, with structural changes, the antifungal effects of these compounds will increase.