{"title":"从海洋真菌文库中筛选、发现和优化天然抗结核氯黄酮。","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":"<p><p>Tuberculosis (TB), caused by the bacterium <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), is still a leading cause of mortality worldwide. Fifty-fungi from a marine-derived fungal library were screened for anti-<i>Mtb</i> activity, and an <i>Aspergillus candidus</i> strain with strong anti-<i>Mtb</i> activity was found. Three known flavones, chlorflavonin (<b>1</b>), dechlorflavonin (<b>2</b>), and bromoflavone (<b>3</b>), were isolated from this fungus. Chlorflavonin and bromoflavone showed inhibitory activity with MIC<sub>90</sub> values of 2.6 and 1.2 <i>μ</i>M, respectively. In combination with molecular docking, a series of new chlorflavonin derivatives (<b>4</b>-<b>41</b>) were rationally designed and semisynthesized. Three new derivatives substituted with (2)-chlorocinnamate (<b>14</b>), (3)-chlorocinnamate (<b>15</b>), and benzoate (<b>18</b>) at position 2' showed MIC<sub>90</sub> values ranging from 0.7 to 1.0 <i>μ</i>M, having the potential to be further explored as antitubercular agents.</p>","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":"{\"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\":\"<p><p>Tuberculosis (TB), caused by the bacterium <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>), is still a leading cause of mortality worldwide. Fifty-fungi from a marine-derived fungal library were screened for anti-<i>Mtb</i> activity, and an <i>Aspergillus candidus</i> strain with strong anti-<i>Mtb</i> activity was found. Three known flavones, chlorflavonin (<b>1</b>), dechlorflavonin (<b>2</b>), and bromoflavone (<b>3</b>), were isolated from this fungus. Chlorflavonin and bromoflavone showed inhibitory activity with MIC<sub>90</sub> values of 2.6 and 1.2 <i>μ</i>M, respectively. In combination with molecular docking, a series of new chlorflavonin derivatives (<b>4</b>-<b>41</b>) were rationally designed and semisynthesized. Three new derivatives substituted with (2)-chlorocinnamate (<b>14</b>), (3)-chlorocinnamate (<b>15</b>), and benzoate (<b>18</b>) at position 2' showed MIC<sub>90</sub> values ranging from 0.7 to 1.0 <i>μ</i>M, having the potential to be further explored as antitubercular agents.</p>\",\"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}","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}
Screening, Discovery, and Optimization of the Natural Antitubercular Chlorflavonin from a Marine-Derived Fungal Library.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
