Institute of Organic Chemistry, Catalysis and Petrochemistry, Slovak University of Technology, Radlinského 9, 812 37 Bratislava, Slovakia.
Institute of Biochemistry and Microbiology, Slovak University of Technology, Radlinského 9, 812 37 Bratislava, Slovakia.
Org Biomol Chem. 2022 Oct 12;20(39):7821-7832. doi: 10.1039/d2ob01452a.
Berkeleylactone A is a potent 16-membered macrolactone antibiotic, recently isolated from a coculture of Berkeley Pit Lake fungi. Although its antimicrobial activity has already been investigated, little is known about the structure-activity relationship. Based on our previous synthetic studies, a series of berkeleylactone A derivatives were synthesized and evaluated for their antimicrobial activities against methicillin-sensitive and methicillin-resistant (MRSA) strains. Our data confirmed the essential role of the embedded conjugated system and suggest a reversible sulfa-protection of the Michael acceptor as a viable option. Structurally simplified achiral macrolactam 8 showed the best inhibitory activity against L12 (MRSA) with MIC values of 0.39 μg mL, 8-fold lower than those of berkeleylactone A. These studies may be of value in the development of more advanced candidates for antibiotic applications.
Berkeleylactone A 是一种强效的 16 元大环内酯抗生素，最近从伯克利坑湖真菌的共培养物中分离得到。尽管其抗菌活性已经得到了研究，但对其结构-活性关系知之甚少。基于我们之前的合成研究，我们合成了一系列伯克利内酯 A 衍生物，并评估了它们对甲氧西林敏感和耐甲氧西林金黄色葡萄球菌（MRSA）菌株的抗菌活性。我们的数据证实了嵌入式共轭系统的重要作用，并表明迈克尔受体的可逆磺胺保护是一种可行的选择。结构简化的非手性大环内酰胺 8 对 L12（MRSA）表现出最好的抑制活性，MIC 值为 0.39 μg mL，比伯克利内酯 A 低 8 倍。这些研究可能对开发更先进的抗生素候选药物具有重要价值。
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