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

Daniele Silva,Laísa Cordeiro,Abrahão Oliveira-Filho,Juliana Souza,Edeltrudes Lima,Maria Morais,Shellygton Silva,Gregório Rodrigues,Thamara Melo,Aleson Sousa,Jefferson Nóbrega,Lyvia Rosa,Helivaldo Souza,Francisco Andrade-Júnior,Maria Silva-Neta,Maria Leite,Hermes Diniz-Neto

doi:10.3390/ijms21051785

Abstract

The enantiomers (R)-(+)-β-citronellol and (S)-(−)-β-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 β-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-(+)-β-citronellol and S-(−)-β-citronellol presented a MIC50% of 64 µg/mL and a MFC50% of 256 µg/mL for C. albicans strains. For C. tropicalis, the isomers exhibited a MIC50% of 256 µg/mL and a MFC50% 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.

Highlights

Optical isomers, or enantiomers, are non-overlapping images which possess the same physicochemical properties, except in the way they deviate polarized light and odor
The occurrence of chirality in natural products is very common, and efforts to understand their biological profiles and origins in biosynthetic pathways are constant [2]. These products present considerable importance to the pharmaceutical industry due to their ability to serve as active molecules or as prototypes for obtaining specific pharmacological and toxicological profiles, which often cannot be obtained without more expensive chemical synthesis [3]
The MIC50% found for R-(+)-β-citronellol was 64 μg/mL and its MFC50% was 256 μg/mL against strains of C. albicans

Summary

Introduction

Enantiomers, are non-overlapping images which possess the same physicochemical properties, except in the way they deviate polarized light and odor. The occurrence of chirality in natural products is very common, and efforts to understand their biological profiles and origins in biosynthetic pathways are constant [2]. These products present considerable importance to the pharmaceutical industry due to their ability to serve as active molecules or as prototypes for obtaining specific pharmacological and toxicological profiles, which often cannot be obtained without more expensive chemical synthesis [3]. Terpenes represent one of the larger classes of secondary metabolites, comprising more than 30,000 compounds Due to their diversity and biological activity, these molecules often make enormous contributions. Namely taxanes, steroids, tocopherols, ingenanes, artemisinins, and cannabinoids, owe their existence to molecules of this class, revealing how much this group has contributed in the last century to both modern medicine, and many different industrial segments [4,5,6,7,8]

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