Investigating the Antifungal Effects of Spirocyclopropane Oxindoles Derivatives Against Aspergillus Species

Introduction: Given the increasing resistance of Aspergillus spp to azoles, it is important to find new compounds that are effective, such as the spirocyclopropane oxindoles (۴a-۴b-۴c) derivatives. The aim of the present study was to evaluate the antifungal activity of spirocyclopropane oxindoles (۴a-۴b-۴c) derivatives against Aspergillus spp. Methods: In vitro cytotoxicity of the synthesized compounds was evaluated against MCF-۷ cancer cell lines using the MTT assay. In the next step, the antifungal susceptibility of ۵۰ Aspergillus isolates of clinical origin to spirocyclopropane oxindoles (۴a-۴b-۴c) derivatives and itraconazole was evaluated according to CLSI M۳۸A۲ guidelines. Statistical analysis was performed using SPSS۲۰ software and the significance level was considered as P < ۰.۰۵. Results:The results revealed that among the three synthesized compounds, ۴c exhibited the lowest toxicity to MCF-۷ cells. However, this level of toxicity was higher than control.  In the present study, there is a significant difference between the MIC values of ۴a-۴b-۴c oxindole derivatives of spirocyclopropane and itraconazole against Aspergillus spp. Comparing the MIC values of ۴a, ۴b and ۴c oxindole spirocyclopropane derivatives with each other (۴a-۴b-۴c), ۴b derivatives have lower MIC values for Aspergillus flavus and Aspergillus fumigatus isolates. In addition, ۴c derivatives had the highest MIC for Aspergillus terreus. Conclusion: Although the antifungal effects of Spirocyclopropane Oxindoles (۴a-۴b-۴c) on Aspergillus spp were significantly lower than itraconazole, but with structural changes, we can hope to increase the antifungal effects of these compounds.

Keywords:

Spirocyclopropane Oxindoles derivatives , itraconazole , Aspergillus