Quan T Khong, Lindsay Marron, Shar-Yin Naomi Huang, Masoumeh Dalilian, Sourav Saha, Ekaterina I Goncharova, Girma M Woldemichael, Yves Pommier, Barry R O'Keefe, Brice A P Wilson, Lin Du
{"title":"马尾草中呋喃heliangolides及柔性手性侧链立体化学配位的一般方法。","authors":"Quan T Khong, Lindsay Marron, Shar-Yin Naomi Huang, Masoumeh Dalilian, Sourav Saha, Ekaterina I Goncharova, Girma M Woldemichael, Yves Pommier, Barry R O'Keefe, Brice A P Wilson, Lin Du","doi":"10.1021/acs.jnatprod.5c00329","DOIUrl":null,"url":null,"abstract":"<p><p>Human topoisomerase 3β (TOP3B) is a potential molecular therapeutic target for cancer and viral infections. A high-throughput differential cell viability assay using colon cancer cell lines was developed to identify natural product modulators of TOP3B-associated cancer cell viability. The assay identified an organic extract of the plant <i>Centratherum punctatum</i> as having cytotoxic activity. Seven new furanoheliangolides, centratherolides A-G (<b>1</b>-<b>7</b>), along with two known analogues (2,3-epoxybutyryloxy)-goyazensolanolide (<b>8</b>) and goyazensolide (<b>9</b>), were isolated. Compounds <b>1</b>, <b>8</b>, and <b>9</b> exhibited selective cytotoxic activities against the TOP3B-knockout (TOP3B-KO) human colon carcinoma HCT116 cells compared with the wild-type HCT116 cells (TOP3B-WT). The challenging absolute configuration determination of the flexible chiral side chains in selected analogues (<b>1</b>-<b>4</b> and <b>8</b>) was resolved by combined approaches, including synthesis of chemical standards, DFT ECD calculation, and chiral HPLC analysis. Application of this elucidation methodology to a commercial sesquiterpene lactone clarified a contradiction in the stereochemical assignments reported for centaurepensin/chlorohyssopifolin A and 17-<i>epi</i>-chlorohyssopifolin A.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"1413-1424"},"PeriodicalIF":3.6000,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Furanoheliangolides from <i>Centratherum punctatum</i> and a General Approach for Stereochemical Assignment of Flexible Chiral Side Chains.\",\"authors\":\"Quan T Khong, Lindsay Marron, Shar-Yin Naomi Huang, Masoumeh Dalilian, Sourav Saha, Ekaterina I Goncharova, Girma M Woldemichael, Yves Pommier, Barry R O'Keefe, Brice A P Wilson, Lin Du\",\"doi\":\"10.1021/acs.jnatprod.5c00329\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Human topoisomerase 3β (TOP3B) is a potential molecular therapeutic target for cancer and viral infections. A high-throughput differential cell viability assay using colon cancer cell lines was developed to identify natural product modulators of TOP3B-associated cancer cell viability. The assay identified an organic extract of the plant <i>Centratherum punctatum</i> as having cytotoxic activity. Seven new furanoheliangolides, centratherolides A-G (<b>1</b>-<b>7</b>), along with two known analogues (2,3-epoxybutyryloxy)-goyazensolanolide (<b>8</b>) and goyazensolide (<b>9</b>), were isolated. Compounds <b>1</b>, <b>8</b>, and <b>9</b> exhibited selective cytotoxic activities against the TOP3B-knockout (TOP3B-KO) human colon carcinoma HCT116 cells compared with the wild-type HCT116 cells (TOP3B-WT). The challenging absolute configuration determination of the flexible chiral side chains in selected analogues (<b>1</b>-<b>4</b> and <b>8</b>) was resolved by combined approaches, including synthesis of chemical standards, DFT ECD calculation, and chiral HPLC analysis. Application of this elucidation methodology to a commercial sesquiterpene lactone clarified a contradiction in the stereochemical assignments reported for centaurepensin/chlorohyssopifolin A and 17-<i>epi</i>-chlorohyssopifolin A.</p>\",\"PeriodicalId\":47,\"journal\":{\"name\":\"Journal of Natural Products \",\"volume\":\" \",\"pages\":\"1413-1424\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-06-27\",\"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.5c00329\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/22 0:00:00\",\"PubModel\":\"Epub\",\"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.5c00329","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/22 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Furanoheliangolides from Centratherum punctatum and a General Approach for Stereochemical Assignment of Flexible Chiral Side Chains.
Human topoisomerase 3β (TOP3B) is a potential molecular therapeutic target for cancer and viral infections. A high-throughput differential cell viability assay using colon cancer cell lines was developed to identify natural product modulators of TOP3B-associated cancer cell viability. The assay identified an organic extract of the plant Centratherum punctatum as having cytotoxic activity. Seven new furanoheliangolides, centratherolides A-G (1-7), along with two known analogues (2,3-epoxybutyryloxy)-goyazensolanolide (8) and goyazensolide (9), were isolated. Compounds 1, 8, and 9 exhibited selective cytotoxic activities against the TOP3B-knockout (TOP3B-KO) human colon carcinoma HCT116 cells compared with the wild-type HCT116 cells (TOP3B-WT). The challenging absolute configuration determination of the flexible chiral side chains in selected analogues (1-4 and 8) was resolved by combined approaches, including synthesis of chemical standards, DFT ECD calculation, and chiral HPLC analysis. Application of this elucidation methodology to a commercial sesquiterpene lactone clarified a contradiction in the stereochemical assignments reported for centaurepensin/chlorohyssopifolin A and 17-epi-chlorohyssopifolin A.
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.
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