• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

一种新颖的番荔枝内酯噻吩-3-甲酰胺类似物通过抑制线粒体复合物I展现出抗肿瘤活性。

A novel thiophene-3-carboxamide analog of annonaceous acetogenin exhibits antitumor activity via inhibition of mitochondrial complex I.

作者信息

Akatsuka Akinobu, Kojima Naoto, Okamura Mutsumi, Dan Shingo, Yamori Takao

机构信息

Molecular Pharmacology Cancer Chemotherapy Center Japanese Foundation for Cancer Research Tokyo Japan.

Pharmaceutical Manufacturing Chemistry Kyoto Pharmaceutical University Kyoto Japan.

出版信息

Pharmacol Res Perspect. 2016 Jul 12;4(4):e00246. doi: 10.1002/prp2.246. eCollection 2016 Aug.

DOI:10.1002/prp2.246
PMID:28116099
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5242172/
Abstract

Previously we synthesized JCI-20679, a novel thiophene-3-carboxamide analog of annonaceous acetogenins which have shown potent antitumor activity, with no serious side effects, in mouse xenograft models. In this study, we investigated the antitumor mechanism of JCI-20679. The growth inhibition profile (termed "fingerprint") of this agent across a panel of 39 human cancer cell lines (termed "JFCR39") was measured; this fingerprint was analyzed by the COMPARE algorithm utilizing the entire drug sensitivity database for the JFCR39 panel. The JCI-20679-specific fingerprint exhibited a high similarity to those of two antidiabetic biguanides and a natural rotenoid deguelin which were already known to be mitochondrial complex I inhibitors. In addition, the fingerprint exhibited by JCI-20679 was not similar to that displayed by any typical anticancer drugs within the database, suggesting that it has a unique mode of action. In vitro experiments using bovine heart-derived mitochondria showed direct inhibition of mitochondrial complex I by JCI-20679 and associated derivatives. This inhibition of enzymatic activity positively correlated with tumor cell growth inhibition. Furthermore, a fluorescently labeled derivative of JCI-20679 localized to the mitochondria of live cancer cells in vitro. These results suggest that JCI-20679 can inhibit cancer cell growth by inhibiting mitochondrial complex I. Our results show that JCI-20679 is a novel anticancer drug lead with a unique mode of action.

摘要

此前我们合成了JCI - 20679，它是番荔枝内酯的一种新型噻吩 - 3 - 甲酰胺类似物，在小鼠异种移植模型中已显示出强效抗肿瘤活性且无严重副作用。在本研究中，我们探究了JCI - 20679的抗肿瘤机制。测定了该药物在一组39种人类癌细胞系（称为“JFCR39”）中的生长抑制谱（称为“指纹图谱”）；利用JFCR39细胞系的整个药物敏感性数据库，通过COMPARE算法对该指纹图谱进行了分析。JCI - 20679特异性指纹图谱与两种抗糖尿病双胍类药物以及一种已知为线粒体复合物I抑制剂的天然鱼藤酮类化合物鱼藤素的指纹图谱高度相似。此外，JCI - 20679呈现的指纹图谱与数据库中任何典型抗癌药物的指纹图谱均不相似，这表明它具有独特的作用模式。使用牛心来源的线粒体进行的体外实验表明，JCI - 20679及其相关衍生物可直接抑制线粒体复合物I。这种酶活性的抑制与肿瘤细胞生长抑制呈正相关。此外，JCI - 20679的一种荧光标记衍生物在体外定位于活癌细胞的线粒体。这些结果表明，JCI - 20679可通过抑制线粒体复合物I来抑制癌细胞生长。我们的结果表明，JCI - 20679是一种具有独特作用模式的新型抗癌药物先导物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/8e632e0a30d6/PRP2-4-0246-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/2a7ce439b477/PRP2-4-0246-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/d98cb30c0c42/PRP2-4-0246-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/09cf60127851/PRP2-4-0246-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/360a11c1e9e7/PRP2-4-0246-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/8e632e0a30d6/PRP2-4-0246-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/2a7ce439b477/PRP2-4-0246-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/d98cb30c0c42/PRP2-4-0246-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/09cf60127851/PRP2-4-0246-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/360a11c1e9e7/PRP2-4-0246-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9906/5242172/8e632e0a30d6/PRP2-4-0246-g005.jpg

相似文献

1
A novel thiophene-3-carboxamide analog of annonaceous acetogenin exhibits antitumor activity via inhibition of mitochondrial complex I.一种新颖的番荔枝内酯噻吩-3-甲酰胺类似物通过抑制线粒体复合物I展现出抗肿瘤活性。
Pharmacol Res Perspect. 2016 Jul 12;4(4):e00246. doi: 10.1002/prp2.246. eCollection 2016 Aug.
2
Structure-Activity Relationships of Thiophene Carboxamide Annonaceous Acetogenin Analogs: Shortening the Alkyl Chain in the Tail Part Significantly Affects Their Growth Inhibitory Activity against Human Cancer Cell Lines.噻吩甲酰胺藤黄烷酮类似物的构效关系：缩短尾部的烷基链显著影响其对人癌细胞系的生长抑制活性。
Chem Pharm Bull (Tokyo). 2021;69(10):1029-1033. doi: 10.1248/cpb.c21-00450.
3
Thiophene-3-carboxamide analogue of annonaceous acetogenins as antitumor drug lead.番荔枝内酯的噻吩-3-甲酰胺类似物作为抗肿瘤药物先导物。
Eur J Med Chem. 2014 Oct 30;86:684-9. doi: 10.1016/j.ejmech.2014.09.026. Epub 2014 Sep 9.
4
Synthesis of dansyl-labeled probe of thiophene analogue of annonaceous acetogenins for visualization of cell distribution and growth inhibitory activity toward human cancer cell lines.用于可视化细胞分布及对人癌细胞系生长抑制活性的番荔枝乙酰精菌素噻吩类似物丹磺酰标记探针的合成。
Bioorg Med Chem. 2015 Mar 15;23(6):1276-83. doi: 10.1016/j.bmc.2015.01.037. Epub 2015 Jan 29.
5
Thiophene Carboxamide Analogs with Long Alkyl Chains Comprising Ethylene Glycol Units Inhibit Glioblastoma Cell Proliferation by Activating AMPK.含乙二醇单元的长链噻吩甲酰胺类似物通过激活 AMPK 抑制神经胶质瘤细胞增殖。
J Med Chem. 2023 May 11;66(9):6403-6413. doi: 10.1021/acs.jmedchem.3c00474. Epub 2023 Apr 28.
6
Critical role of a methyl group on the γ-lactone ring of annonaceous acetogenins in the potent inhibition of mitochondrial complex I.γ-内酯环上的甲基在番荔枝烷型乙酰辅酶 A 合酶抑制剂抑制线粒体复合体 I 活性中具有关键作用。
Bioorg Med Chem Lett. 2013 Mar 1;23(5):1217-9. doi: 10.1016/j.bmcl.2013.01.018. Epub 2013 Jan 12.
7
Synthesis and inhibitory action of novel acetogenin mimics with bovine heart mitochondrial complex I.新型产乙酸素类似物与牛心线粒体复合物I的合成及抑制作用
Biochemistry. 2004 Mar 30;43(12):3651-8. doi: 10.1021/bi030242m.
8
Convergent synthesis of fluorescence-labeled probes of Annonaceous acetogenins and visualization of their cell distribution.荧光标记的番荔枝内酯类生物合成探针的汇聚合成及其细胞分布可视化。
Bioorg Med Chem. 2010 Dec 15;18(24):8630-41. doi: 10.1016/j.bmc.2010.10.004. Epub 2010 Oct 16.
9
Structure-antitumor activity relationship of hybrid acetogenins focusing on connecting groups between heterocycles and the linker moiety.聚焦杂环与连接基团之间连接部分的杂合产乙酸菌素的结构-抗肿瘤活性关系
RSC Adv. 2022 May 25;12(25):15728-15739. doi: 10.1039/d2ra02399g. eCollection 2022 May 23.
10
In vitro antitumor structure-activity relationships of threo/trans/threo/trans/erythro bis-tetrahydrofuranic acetogenins: correlations with their inhibition of mitochondrial complex I.苏式/反式/苏式/反式/赤式双四氢呋喃型产乙酸菌素的体外抗肿瘤构效关系：与其对线粒体复合物I的抑制作用的相关性
Oncol Res. 2005;15(3):129-38. doi: 10.3727/096504005776367915.

引用本文的文献

1
Novel Compounds Featuring a Thiophene Carboxamide Scaffold: Synthesis, Characterization and Antiproliferative Evaluation.具有噻吩甲酰胺骨架的新型化合物：合成、表征及抗增殖评估
Int J Mol Sci. 2025 Jul 16;26(14):6823. doi: 10.3390/ijms26146823.
2
Targeting Oxidative Phosphorylation with a Novel Thiophene Carboxamide Increases the Efficacy of Imatinib against Leukemic Stem Cells in Chronic Myeloid Leukemia.靶向氧化磷酸化的新型噻吩甲酰胺提高伊马替尼治疗慢性髓性白血病白血病干细胞的疗效。
Int J Mol Sci. 2024 Oct 15;25(20):11093. doi: 10.3390/ijms252011093.
3
Insights into Molecular Mechanisms of Anticancer Activity of Essential Oil in HeLa and HCT 116 Cells.

本文引用的文献

1
Synthesis of dansyl-labeled probe of thiophene analogue of annonaceous acetogenins for visualization of cell distribution and growth inhibitory activity toward human cancer cell lines.用于可视化细胞分布及对人癌细胞系生长抑制活性的番荔枝乙酰精菌素噻吩类似物丹磺酰标记探针的合成。
Bioorg Med Chem. 2015 Mar 15;23(6):1276-83. doi: 10.1016/j.bmc.2015.01.037. Epub 2015 Jan 29.
2
Thiophene-3-carboxamide analogue of annonaceous acetogenins as antitumor drug lead.番荔枝内酯的噻吩-3-甲酰胺类似物作为抗肿瘤药物先导物。
Eur J Med Chem. 2014 Oct 30;86:684-9. doi: 10.1016/j.ejmech.2014.09.026. Epub 2014 Sep 9.
3
Structure-activity relationships of hybrid annonaceous acetogenins: powerful growth inhibitory effects of their connecting groups between heterocycle and hydrophobic carbon chain bearing THF ring on human cancer cell lines.
精油对HeLa和HCT 116细胞抗癌活性的分子机制洞察。
Plants (Basel). 2024 Aug 23;13(17):2351. doi: 10.3390/plants13172351.
4
A study on the cellular and cytotoxic effects of S and Se heterocycles on the myeloid leukemia cell line PLB-985.S和Se杂环对髓系白血病细胞系PLB-985的细胞及细胞毒性作用的研究
Phosphorus Sulfur Silicon Relat Elem. 2022;197(8):876-884. doi: 10.1080/10426507.2022.2085272. Epub 2022 Jun 9.
5
Structure-antitumor activity relationship of hybrid acetogenins focusing on connecting groups between heterocycles and the linker moiety.聚焦杂环与连接基团之间连接部分的杂合产乙酸菌素的结构-抗肿瘤活性关系
RSC Adv. 2022 May 25;12(25):15728-15739. doi: 10.1039/d2ra02399g. eCollection 2022 May 23.
6
Mechanistic study of PpIX accumulation using the JFCR39 cell panel revealed a role for dynamin 2-mediated exocytosis.使用 JFCR39 细胞系进行 PpIX 积累的机制研究揭示了胞吐作用的作用，胞吐作用是由动力蛋白 2 介导的。
Sci Rep. 2019 Jun 17;9(1):8666. doi: 10.1038/s41598-019-44981-y.
7
Inducing cancer indolence by targeting mitochondrial Complex I is potentiated by blocking macrophage-mediated adaptive responses.靶向线粒体复合物 I 诱导癌症惰性会增强巨噬细胞介导的适应性反应的阻断作用。
Nat Commun. 2019 Feb 22;10(1):903. doi: 10.1038/s41467-019-08839-1.
8
Metabolic Profiles Associated With Metformin Efficacy in Cancer.与二甲双胍在癌症治疗中的疗效相关的代谢谱
Front Endocrinol (Lausanne). 2018 Aug 21;9:372. doi: 10.3389/fendo.2018.00372. eCollection 2018.
9
The Paradigm of Respiratory Complex I.呼吸复合体I的范式
Genes (Basel). 2018 May 7;9(5):243. doi: 10.3390/genes9050243.
10
Mitochondrial Complex I Inhibitors Expose a Vulnerability for Selective Killing of Pten-Null Cells.线粒体复合物 I 抑制剂暴露了选择性杀死 Pten 缺失细胞的脆弱性。
Cell Rep. 2018 Apr 3;23(1):58-67. doi: 10.1016/j.celrep.2018.03.032.
杂合型番荔枝烷型二萜类化合物的构效关系：杂环与带有四氢呋喃环的疏碳链连接基团对人癌细胞系的强大生长抑制作用。
Eur J Med Chem. 2013 May;63:833-9. doi: 10.1016/j.ejmech.2013.03.009. Epub 2013 Mar 14.
4
AMF-26, a novel inhibitor of the Golgi system, targeting ADP-ribosylation factor 1 (Arf1) with potential for cancer therapy.AMF-26，一种新型的高尔基系统抑制剂，靶向 ADP-ribosylation factor 1（Arf1），具有癌症治疗的潜力。
J Biol Chem. 2012 Feb 3;287(6):3885-97. doi: 10.1074/jbc.M111.316125. Epub 2011 Dec 9.
5
Targeting mitochondria for cancer therapy.针对线粒体的癌症治疗方法。
Nat Rev Drug Discov. 2010 Jun;9(6):447-64. doi: 10.1038/nrd3137. Epub 2010 May 14.
6
Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner.二甲双胍不依赖于 AMPK，以 rag GTPase 依赖性方式抑制 mTORC1。
Cell Metab. 2010 May 5;11(5):390-401. doi: 10.1016/j.cmet.2010.03.014.
7
Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity.牛蒡子苷元阻断未折叠蛋白反应并显示出治疗抗肿瘤活性。
J Cell Physiol. 2010 Jul;224(1):33-40. doi: 10.1002/jcp.22085.
8
Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions.线粒体调节未折叠蛋白反应，导致癌细胞在葡萄糖缺乏条件下存活。
Cancer Sci. 2010 May;101(5):1125-32. doi: 10.1111/j.1349-7006.2010.01525.x. Epub 2010 Feb 5.
9
Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway.地榆苷通过调节 Wnt 信号通路关键成员的表达抑制乳腺癌细胞的生长。
Cancer Prev Res (Phila). 2009 Nov;2(11):942-50. doi: 10.1158/1940-6207.CAPR-08-0232. Epub 2009 Oct 27.
10
Medicinal chemistry of Annonaceous acetogenins: design, synthesis, and biological evaluation of novel analogues.番荔枝科乙酰精宁的药物化学：新型类似物的设计、合成及生物学评价
Molecules. 2009 Sep 17;14(9):3621-61. doi: 10.3390/molecules14093621.