Laboratory of Molecular Genetics of Microorganisms, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan 420008, Russia.
Industrial Drug Technology and Biotechnology, Perm State Pharmaceutical Academy, Perm 614990, Russia.
Molecules. 2020 Feb 2;25(3):642. doi: 10.3390/molecules25030642.
The frequency of mycoses caused by drug-resistant fungal pathogen has increased drastically over the last two decades. The spread of drug-resistant strains, along with the limitations of currently available antifungals, complicates the management of fungal infections, thereby representing great challenges for clinical healthcare. Among various antimicrobial pharmacophores, 2(5)-furanone derivatives have demonstrated antimicrobial, antifungal, and antibiofilm activities. In this study, we report the antifungal activity of the 2(5)-furanone derivative , consisting of three pharmacophores, namely chlorinated 2(5)-furanone, sulfonyl group, and -menthol moiety. Although exhibiting moderate antifungal activity alone with the minimum inhibitory concentration (MIC) values of 32-256 μg/mL, potentiates the activity of fluconazole and terbinafine with fractional inhibitory concentration index (FICI) values of 0.27-0.50. Thus, 16 μg/mL of reduced the MICs of these antifungals against fluconazole-resistant isolates four-fold, achieving similar values as for the intermediately susceptible phenotype. Confocal laser scanning microscopy revealed that the fluorescent 2(5)-furanone derivative was also able to penetrate through biofilms formed by . Indeed, in the presence of , even sub-MIC concentrations of both fluconazole and terbinafine led to significant reduction of CFUs in the mature biofilm. Thus, appears to be a promising candidate for the development of novel antifungal agents as well as enhancers of current antifungal agents, particularly for the treatment of drug-resistant infections.
在过去的二十年中，由耐药真菌病原体引起的真菌感染的频率急剧增加。耐药菌株的传播以及现有抗真菌药物的局限性，使真菌感染的管理变得复杂，从而给临床医疗保健带来了巨大挑战。在各种抗菌药效团中，2(5)-呋喃酮衍生物表现出抗菌、抗真菌和抗生物膜活性。在这项研究中，我们报告了由三个药效团组成的 2(5)-呋喃酮衍生物的抗真菌活性，这三个药效团分别是氯化 2(5)-呋喃酮、磺酰基和 -薄荷醇部分。虽然单独使用时具有中等的抗真菌活性，最低抑菌浓度（MIC）值为 32-256μg/mL，但它增强了氟康唑和特比萘芬的活性，其部分抑菌浓度指数（FICI）值为 0.27-0.50。因此，16μg/mL 的 使这些抗真菌药物对氟康唑耐药 分离株的 MIC 值降低了四倍，达到与中间敏感表型相似的值。共聚焦激光扫描显微镜显示，荧光 2(5)-呋喃酮衍生物 也能够穿透 形成的生物膜。事实上，在 的存在下，即使是氟康唑和特比萘芬的亚 MIC 浓度也能显著减少成熟生物膜中的 CFU。因此， 似乎是开发新型抗真菌药物以及增强现有抗真菌药物的有前途的候选药物，特别是用于治疗耐药 感染。
