Department of Molecular Biotechnology and Microbiology, University of Debrecen, 4010 Debrecen, Hungary.
Molecules. 2020 May 21;25(10):2401. doi: 10.3390/molecules25102401.
Gentamicin is a broad-spectrum aminoglycoside antibiotic produced by bacteria, effective against Gram-negative bacterial infections. Major fractions of the gentamicin complex (C1, C1a, C2, C2a) possess weak antifungal activity and one of the minor components (A, A1-A4, B, B1, X), gentamicin B1 was found to be a strong antifungal agent.
This work uses in vitro and in vivo dilution methods to compare the antifusarial, antiaspergillic and anticryptococcal effects of gentamicin derivatives and structurally-related congeners.
The in vitro antifusarial activity of gentamicin B1 (minimum inhibitory concentration (MIC) 0.4 μg/mL) and structurally-related compounds (MIC 0.8-12.5 μg/mL) suggests that the purpuroseamine ring substituents are responsible for the specific antimycotic effect. The functional groups of the garoseamine and 2-deoxystreptamine rings of gentamicin derivatives are identical in gentamicin compounds and are unlikely to exert a significant antifungal effect. Among soil dermatophytes, was more susceptible to gentamicin B1 (MIC 3.1 µg/mL) than (MIC 25 µg/mL). The in vitro antifungal effect of gentamicin B1 against plant pathogenic fungi was comparable to primary antifungal agents.
Gentamicin is already in medical use. In vitro and preclinical in vivo synergisms of gentamicin B1 with amphotericin B suggest immediate clinical trials starting with subtoxic doses.
庆大霉素是一种由细菌产生的广谱氨基糖苷类抗生素，对革兰氏阴性菌感染有效。庆大霉素复合物的主要成分（C1、C1a、C2、C2a）具有较弱的抗真菌活性，其中一个次要成分（A、A1-A4、B、B1、X），庆大霉素 B1 被发现具有很强的抗真菌活性。
本研究采用体外和体内稀释法比较了庆大霉素衍生物和结构相关类似物的抗真菌、抗曲霉和抗隐球菌作用。
庆大霉素 B1（最低抑菌浓度（MIC）0.4μg/mL）和结构相关化合物（MIC 0.8-12.5μg/mL）的体外抗真菌活性表明，紫素环取代基是产生特定抗真菌作用的原因。庆大霉素衍生物的胍醇和 2-去氧链霉胺环的功能基团在庆大霉素化合物中是相同的，不太可能产生显著的抗真菌作用。在土壤皮肤真菌中，对庆大霉素 B1（MIC3.1μg/mL）的敏感性高于对（MIC25μg/mL）的敏感性。庆大霉素 B1 对植物病原真菌的体外抗真菌作用与主要抗真菌药物相当。
庆大霉素已在医学上使用。庆大霉素 B1 与两性霉素 B 的体外和临床前体内协同作用表明，应立即开始用亚毒性剂量进行临床试验。
