{"title":"Cytotoxic diterpenoids from Croton kongensis inhibiting tumor proliferation and migration","authors":"","doi":"10.1016/j.bioorg.2024.107739","DOIUrl":null,"url":null,"abstract":"<div><p>Thirty-two diterpenoids including 18 <em>ent</em>-kauranes (<strong>1</strong>–<strong>6</strong>, and <strong>12</strong>–<strong>23</strong>), nine 8,9-<em>seco-ent</em>-kauranes (<strong>7</strong>–<strong>8</strong>, and <strong>24</strong>–<strong>30</strong>), four <em>ent</em>-abietanes (<strong>9</strong>–<strong>10</strong>, and <strong>31</strong>–<strong>32</strong>), and one crotofolane (<strong>11</strong>) were isolated from the twigs and leaves of <em>Croton kongensis</em>. The structures of previously unreported crokokaugenoids A–H (<strong>1</strong>–<strong>8</strong>), crokoabiegenoids A–B (<strong>9</strong>–<strong>10</strong>), and crokocrotogenoid A (<strong>11</strong>) were determined by spectroscopic data analyses, TDDFT-ECD and GIAO NMR calculations, and X-ray crystallographic studies. All compounds were evaluated for their cytotoxic activity against five human tumor cell lines, and the structure–activity relationships were discussed. Biological tests exhibited that compound <strong>1</strong> possessed strong anti-proliferation activity, arrested cell cycle at G2/M phase, and induced cell apoptosis of MDA-MB-231. The mechanism investigation showed that compound <strong>1</strong> can inhibit tumor proliferation and migration by targeting mitochondria to increase intracellular reactive oxygen species (ROS) and regulating STAT3 and FAK signal pathways. Collectively, these findings supported the great potential of compound <strong>1</strong> as a hopeful anticancer agent.</p></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0045206824006448","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Thirty-two diterpenoids including 18 ent-kauranes (1–6, and 12–23), nine 8,9-seco-ent-kauranes (7–8, and 24–30), four ent-abietanes (9–10, and 31–32), and one crotofolane (11) were isolated from the twigs and leaves of Croton kongensis. The structures of previously unreported crokokaugenoids A–H (1–8), crokoabiegenoids A–B (9–10), and crokocrotogenoid A (11) were determined by spectroscopic data analyses, TDDFT-ECD and GIAO NMR calculations, and X-ray crystallographic studies. All compounds were evaluated for their cytotoxic activity against five human tumor cell lines, and the structure–activity relationships were discussed. Biological tests exhibited that compound 1 possessed strong anti-proliferation activity, arrested cell cycle at G2/M phase, and induced cell apoptosis of MDA-MB-231. The mechanism investigation showed that compound 1 can inhibit tumor proliferation and migration by targeting mitochondria to increase intracellular reactive oxygen species (ROS) and regulating STAT3 and FAK signal pathways. Collectively, these findings supported the great potential of compound 1 as a hopeful anticancer agent.
期刊介绍：
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
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