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The Sensitivity Modifying Activity of Nerolidol and α-Bisabolol Against Trichophyton spp
Indian Journal of Microbiology ( IF 2.1 ) Pub Date : 2020-06-13 , DOI: 10.1007/s12088-020-00895-2
Josenildo Cândido de Oliveira 1 , Ânderson de Vasconcelos Pinto 1 , César Augusto Costa de Medeiros 1 , Hellen Aparecida Silva Ponte 1 , Fillipe de Oliveira Pereira 1
Affiliation  

Trichophyton spp. is one of the main causative agents of dermatophytosis such as tinea ungium and tinea pedis. Resistance to antifungal drugs is a significant clinical problem in dermatophytosis. The main molecular mechanism of antifungal resistance to conventional therapy in dermatophytes is the expression of efflux pumps. Efforts aimed at improving the efficacy of current antifungals such as griseofulvin are relevant. Given this, sesquiterpenes such as α-bisabolol and nerolidol found in essential oils represent promissing alternatives. Griseofulvin sensitivity modulation activity in T. rubrum, T. interdigitale H6, and T. interdigitale Δmdr2 (mutant strain of T. interdigitale) promoted by α-bisabolol and nerolidol were investigated. The minimum inhibitory concentration (MIC) of the test drugs were determined by microdilution. Subsequently, the effect of the drugs tested on plasma membrane functionality (K+ release) was analyzed. The MIC of griseofulvin was determined at sub-inhibitory sesquiterpene concentrations (modulation assay). An association study was performed with griseofulvin and sesquiterpenes (checkerboard). α-bisabolol was more potent than nerolidol; presenting lower MIC values. All of the fungi were sensitive to griseofulvin, starting at 8 µg/mL. With the exception of griseofulvin, all of the test drugs increased K+ release (p < 0.05). Nerolidol modulated the sensitivity of all strains to griseofulvin; α-bisabolol sensitivity modulation was limited to T. interdigitale H6 and T. interdigitale Δmdr2. In association with griseofulvin: nerolidol and α-bisabolol respectively presented synergism and additivity. Finally, the results of our study suggest using α-bisabolol and nerolidol compounds as potential antifungal agents and griseofulvin sensitivity modulators for Trichophyton spp.



中文翻译:

橙花醇和α-红没药醇对毛癣菌属的敏感性调节活性

毛癣菌属 是甲癣足癣等皮肤癣菌病的主要病原体之一。抗真菌药物的耐药性是皮肤癣菌病的一个重要临床问题。皮肤癣菌对常规治疗产生抗真菌耐药性的主要分子机制是外排泵的表达。旨在提高当前抗真菌药(如灰黄霉素)功效的努力是相关的。鉴于此,在精油中发现的倍半萜类化合物,如 α-没药醇和橙花油醇代表了有希望的替代品。在灰黄霉素灵敏度调节活性红色毛癣菌,趾间T. H6,和T.趾间Δmdr2(突变株T.趾间) 由 α-没药醇和橙花醇促进的研究。受试药物的最低抑菌浓度 (MIC) 由微量稀释法确定。随后,分析了测试的药物对质膜功能(K +释放)的影响。灰黄霉素的 MIC 在亚抑制倍半萜浓度下测定(调节试验)。用灰黄霉素和倍半萜(棋盘)进行了一项关联研究。α-没药醇比橙花醇更有效;呈现较低的 MIC 值。所有真菌都对灰黄霉素敏感,起始浓度为 8 µg/mL。除灰黄霉素外,所有试验药物均增加 K +释放(p < 0.05)。橙花醇调节所有菌株对灰黄霉素的敏感性;α-红没药醇敏感性调制仅限于T. interdigitale H6 和T. interdigitale Δmdr2。与灰黄霉素联合:橙花醇和α-没药醇分别呈现协同作用和相加作用。最后,我们的研究结果表明,使用 α-没药醇和橙花醇化合物作为毛癣菌属的潜在抗真菌剂和灰黄霉素敏感性调节剂。

更新日期:2020-06-13
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