Screening, Discovery, and Optimization of the Natural Antitubercular Chlorflavonin from a Marine-Derived Fungal Library.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2025-01-15 DOI:10.1021/acs.jnatprod.4c01374

Cui-Fang Wang, Wen-Hui Wang, Ying Xu, Qun Zhang, Mei-Yan Wei, Yu-Cheng Gu, Tong-Yi Xu, Chang-Lun Shao

{"title":"Screening, Discovery, and Optimization of the Natural Antitubercular Chlorflavonin from a Marine-Derived Fungal Library.","authors":"Cui-Fang Wang, Wen-Hui Wang, Ying Xu, Qun Zhang, Mei-Yan Wei, Yu-Cheng Gu, Tong-Yi Xu, Chang-Lun Shao","doi":"10.1021/acs.jnatprod.4c01374","DOIUrl":null,"url":null,"abstract":"Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is still a leading cause of mortality worldwide. Fifty-fungi from a marine-derived fungal library were screened for anti-Mtb activity, and an Aspergillus candidus strain with strong anti-Mtb activity was found. Three known flavones, chlorflavonin (1), dechlorflavonin (2), and bromoflavone (3), were isolated from this fungus. Chlorflavonin and bromoflavone showed inhibitory activity with MIC90 values of 2.6 and 1.2 μM, respectively. In combination with molecular docking, a series of new chlorflavonin derivatives (4-41) were rationally designed and semisynthesized. Three new derivatives substituted with (2)-chlorocinnamate (14), (3)-chlorocinnamate (15), and benzoate (18) at position 2' showed MIC90 values ranging from 0.7 to 1.0 μM, having the potential to be further explored as antitubercular agents.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jnatprod.4c01374","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is still a leading cause of mortality worldwide. Fifty-fungi from a marine-derived fungal library were screened for anti-Mtb activity, and an Aspergillus candidus strain with strong anti-Mtb activity was found. Three known flavones, chlorflavonin (1), dechlorflavonin (2), and bromoflavone (3), were isolated from this fungus. Chlorflavonin and bromoflavone showed inhibitory activity with MIC₉₀ values of 2.6 and 1.2 μM, respectively. In combination with molecular docking, a series of new chlorflavonin derivatives (4-41) were rationally designed and semisynthesized. Three new derivatives substituted with (2)-chlorocinnamate (14), (3)-chlorocinnamate (15), and benzoate (18) at position 2' showed MIC₉₀ values ranging from 0.7 to 1.0 μM, having the potential to be further explored as antitubercular agents.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

从海洋真菌文库中筛选、发现和优化天然抗结核氯黄酮。

由结核分枝杆菌（Mtb）引起的结核病（TB）仍然是世界范围内导致死亡的主要原因。从海洋真菌文库中筛选了50种真菌的抗结核分枝杆菌活性，发现了一株具有较强抗结核分枝杆菌活性的念珠曲霉。从该真菌中分离得到氯黄酮(1)、脱氯黄酮(2)和溴黄酮(3)3种已知黄酮。氯黄酮和溴黄酮的MIC90值分别为2.6 μM和1.2 μM。结合分子对接，合理设计和半合成了一系列新的氯黄酮衍生物（4-41）。(2)-氯肉桂酸酯（14）、(3)-氯肉桂酸酯（15）和苯甲酸酯（18）在2′位置取代的3个新衍生物MIC90值在0.7 ~ 1.0 μM之间，具有进一步开发抗结核药物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.