Abstract: Objective In order to find antifungal compounds with new structure, the antifungal activity of small G protein inhibitors were tested in vitro. Methods Micro-dilution method was used to investigate the minimum inhibitory concentration (MIC) of different small G protein inhibitors against Candida. After that, the more active compounds were selected for the further antifungal spectrum determination. Time-growth curves and time-kill curves were used to investigate the effect of CASIN on the growth and proliferation of Candida albicans. Hyphae formation experiment was used to investigate the inhibitory effect of compound CASIN on the formation of Candida albicans hyphae. XTT was used to investigate the inhibitory effect of compound CASIN on the formation of Candida albicans biofilms. Results Among the investigated small G protein inhibitors, CASIN had the strongest in vitro antifungal activity. It also had a good inhibitory effect on Candida parapsilosis, Candida krusei, Candida tropicalis, and Candida glabrata with the MIC of 8-16 μg/mL. 16 μg/mL of CASIN could effectively inhibit the growth and proliferation of Candida albicans in YPD medium, and also exhibited fungicidal activity against Candida albicans in RPMI1640 medium. The hyphae formation of Candida albicans was significantly inhibited by 8 μg/mL of CASIN. 8 μg/mL of CASIN had an inhibition rate of more than 80% for the biofilms formation of Candida albicans. Conclusion CASIN, a small G protein inhibitor, has strong antifungal activity in vitro.

Key words: small G protein, CASIN, antifungal