(R)-(+)-β-Citronellol and (S)-(-)-β-Citronellol in Combination with Amphotericin B against Candida Spp.

The enantiomers (R)-(+)-beta-citronellol and (S)-(-)-beta-citronellol are present in many medicinal plants, but little is understood about their bioactivity against Candida yeasts. This study aimed to evaluate the behavior of positive and negative enantiomers of beta-citronellol on strains of Candida albicans and C. tropicalis involved in candidemia. The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined. The evaluation of growth kinetics, mechanism of action, and association studies with Amphotericin B (AB) using the checkerboard method was also performed. R-(+)-beta-citronellol and S-(-)-beta-citronellol presented a MIC50% of 64 mu g/mL and a MFC50% of 256 mu g/mL for C. albicans strains. For C. tropicalis, the isomers exhibited a MIC50% of 256 mu g/mL and a MFC50% of 1024 mu g/mL. In the mechanism of action assay, both substances displayed an effect on the fungal membrane but not on the fungal cell wall. Synergism and indifference were observed in the association of R-(+)-beta-citronellol and AB, while the association between S-(-)-beta-citronellol and AB displayed synergism, additivity, and indifference. In conclusion, both isomers of beta-citronellol presented a similar profile of antifungal activity. Hence, they can be contemplated in the development of new antifungal drugs providing that further research is conducted about their pharmacology and toxicity.