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

Abstract

The enantiomers (R)-(+)-β-citronellol and (S)-(-)-β-citronellol are present in many medicinal plants, but little is understood about their bioactivity against <i>Candida</i> yeasts. This study aimed to evaluate the behavior of positive and negative enantiomers of β-citronellol on strains of <i>Candida albicans</i> and <i>C. tropicalis</i> 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-(+)-β-citronellol and S-(-)-β-citronellol presented a MIC_50% of 64 µg/mL and a MFC_50% of 256 µg/mL for <i>C. albicans</i> strains. For <i>C. tropicalis</i>, the isomers exhibited a MIC_50% of 256 µg/mL and a MFC_50% of 1024 µg/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-(+)-β-citronellol and AB, while the association between S-(-)-β-citronellol and AB displayed synergism, additivity, and indifference. In conclusion, both isomers of β-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.