A new polycyclic tetramate macrolactam from Allostreptomyces RD068384: stereochemistry and antifungal potential

IF 2.1 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal of Antibiotics Pub Date : 2024-04-09 DOI:10.1038/s41429-024-00705-7
Marwa Elsbaey, Yuki Samaru, Engy Elekhnawy, Naoya Oku, Yasuhiro Igarashi
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Abstract

A new polycyclic tetramate macrolactam designated allostreptamide (1), together with four known congeners, were isolated from the culture extract of Allostreptomyces RD068384. The planar structure of the new compound was elucidated through interpretation of NMR and MS data. The absolute configuration was determined through ROESY and ECD analyses. The isolated compounds revealed antifungal potential against fourteen Candida albicans isolates with minimum inhibitory concentrations (MICs) ranging from 64 to 2048 µg ml-1. Compound 3 showed antibiofilm action and considerably reduced the viability of five isolates (36%) in the formed biofilm. The qRT-PCR revealed that 3 downregulated the BCR1, PLB2, ALS1, and SAP5 biofilm related gene expression. Therefore, 3 could be a promising antifungal therapy for C. albicans infections.

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来自全长链霉菌 RD068384 的一种新的多环四元大内酰胺:立体化学和抗真菌潜力
从异链霉 RD068384 的培养提取物中分离出一种新的多环四元大内酰胺,命名为异链霉酰胺(1),以及四种已知的同系物。通过解释核磁共振和质谱数据,阐明了新化合物的平面结构。通过 ROESY 和 ECD 分析确定了绝对构型。分离出的化合物显示出对十四种白色念珠菌分离物的抗真菌潜力,最低抑菌浓度(MICs)为 64 至 2048 µg ml-1。化合物 3 具有抗生物膜作用,可显著降低已形成生物膜的五个分离菌株(36%)的存活率。qRT-PCR 显示,3 下调了 BCR1、PLB2、ALS1 和 SAP5 等生物膜相关基因的表达。因此,3 可以作为一种治疗白僵菌感染的抗真菌疗法。
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来源期刊
Journal of Antibiotics
Journal of Antibiotics 医学-免疫学
CiteScore
6.60
自引率
3.00%
发文量
87
审稿时长
1 months
期刊介绍: The Journal of Antibiotics seeks to promote research on antibiotics and related types of biologically active substances and publishes Articles, Review Articles, Brief Communication, Correspondence and other specially commissioned reports. The Journal of Antibiotics accepts papers on biochemical, chemical, microbiological and pharmacological studies. However, studies regarding human therapy do not fall under the journal’s scope. Contributions regarding recently discovered antibiotics and biologically active microbial products are particularly encouraged. Topics of particular interest within the journal''s scope include, but are not limited to, those listed below: Discovery of new antibiotics and related types of biologically active substances Production, isolation, characterization, structural elucidation, chemical synthesis and derivatization, biological activities, mechanisms of action, and structure-activity relationships of antibiotics and related types of biologically active substances Biosynthesis, bioconversion, taxonomy and genetic studies on producing microorganisms, as well as improvement of production of antibiotics and related types of biologically active substances Novel physical, chemical, biochemical, microbiological or pharmacological methods for detection, assay, determination, structural elucidation and evaluation of antibiotics and related types of biologically active substances Newly found properties, mechanisms of action and resistance-development of antibiotics and related types of biologically active substances.
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