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一株深海热液沉积物真菌 JWM29-10-1 产生的新聚酮化合物及其抑菌活性。

New Polyketides from a Hydrothermal Vent Sediment Fungus sp. JWM29-10-1 and Their Antimicrobial Effects.

机构信息

Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, China.

Helicobacter pylori Research Centre, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing 211166, China.

出版信息

Mar Drugs. 2022 Nov 16;20(11):720. doi: 10.3390/md20110720.

Abstract

Marine fungi-derived secondary metabolites are still an important source for the discovery of potential antimicrobial agents. Here, five new polyketides (, , and -) and seven known compounds (- and -) were obtained from the culture of the marine-derived fungus sp. JWM29-10-1. Their structures were identified by extensive spectrographic data analyses, including 1D and 2D NMR, UV, IR, and HR-ESI-MS. Further, the absolute configurations of new compounds were determined by circular dichroism (CD) spectrum and alkali-hydrolysis in combination with the in situ dimolybdenum CD method. Subsequently, the antimicrobial effects of these isolated compounds were assessed by examining the minimal inhibition concentration (MIC) with the broth microdilution assay. Compounds and exhibited potent antimicrobial activity against , including multidrug-resistant strains, with MIC range values of 2-8 µg/mL. Moreover, compound showed significant inhibitory effects on the growth of Gram-positive pathogens, including methicillin-resistant (MRSA), , and vancomycin-resistant , which greatly threaten human health. This study demonstrates that chromone derivatives -, especially for , could be potential lead compounds for the development of new antimicrobial agents and provides insight for future medicinal chemistry research.

摘要

海洋真菌来源的次生代谢产物仍然是发现潜在抗菌剂的重要来源。在这里,从海洋来源的真菌 sp. JWM29-10-1 的培养物中获得了五个新的聚酮化合物(、、和-)和七个已知化合物(-和-)。通过广泛的光谱数据分析,包括 1D 和 2D NMR、UV、IR 和 HR-ESI-MS,确定了它们的结构。此外,通过圆二色性(CD)光谱和碱水解结合原位二钼 CD 方法确定了新化合物的绝对构型。随后,通过肉汤微量稀释法测定最小抑制浓度(MIC)评估了这些分离化合物的抗菌效果。化合物和对包括多药耐药株在内的具有 MIC 范围值为 2-8 µg/mL 的强大抗菌活性。此外,化合物对包括耐甲氧西林金黄色葡萄球菌(MRSA)、和万古霉素耐药肠球菌在内的革兰氏阳性病原体的生长具有显著的抑制作用,这些病原体对人类健康构成了巨大威胁。本研究表明,色酮衍生物-,特别是对于,可能是开发新型抗菌剂的潜在先导化合物,并为未来的药物化学研究提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b2/9697660/e7afd9023ff9/marinedrugs-20-00720-g001.jpg

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