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(R)-(+)-β-香茅醇和(S)-(-)-β-香茅醇与两性霉素 B 联合治疗念珠菌属

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

机构信息

Postgraduate Program in Bioactive Natural and Synthetic Products, Federal University of Paraíba, João Pessoa 58051-970, Brazil.

Department of Chemistry, Federal University of Paraíba, João Pessoa 58051-970, Brazil.

出版信息

Int J Mol Sci. 2020 Mar 5;21(5):1785. 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 yeasts. This study aimed to evaluate the behavior of positive and negative enantiomers of β-citronellol on strains of and 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 of 64 µg/mL and a MFC of 256 µg/mL for strains. For , the isomers exhibited a MIC of 256 µg/mL and a MFC 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.

摘要

(R)-(+)-β-香茅醇和(S)-(-)-β-香茅醇是许多药用植物中的对映异构体,但对它们对酵母的生物活性知之甚少。本研究旨在评估β-香茅醇的正、负对映异构体对参与念珠菌血症的和的菌株的行为。测定了最小抑菌浓度(MIC)和最低杀菌浓度(MFC)。还进行了生长动力学评估、作用机制评估以及与两性霉素 B(AB)的棋盘法联合研究。R-(+)-β-香茅醇和 S-(-)-β-香茅醇对株的 MIC 为 64 µg/mL,MFC 为 256 µg/mL。对于,这些异构体的 MIC 为 256 µg/mL,MFC 为 1024 µg/mL。在作用机制试验中,两种物质均对真菌膜有作用,但对真菌细胞壁无作用。在 R-(+)-β-香茅醇和 AB 的联合作用中观察到协同作用和无关性,而 S-(-)-β-香茅醇和 AB 的联合作用则显示出协同作用、相加作用和无关性。总之,β-香茅醇的两种对映异构体表现出相似的抗真菌活性。因此,它们可以考虑用于开发新的抗真菌药物,前提是对它们的药理学和毒性进行进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8648/7084460/cd46b05a1f1c/ijms-21-01785-g001.jpg

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