https://scholars.lib.ntu.edu.tw/handle/123456789/597285
標題: | Discovery of a novel series of quinolone and naphthyridine derivatives as potential topoisomerase I inhibitors by scaffold modification | 作者: | You Q.-D. Li Z.-Y. Huang C.-H. Yang Q. Wang X.-J. Guo Q.-L. Chen X.-G. He X.-G. TSAI-KUN LI Chern J.-W. |
公開日期: | 2009 | 卷: | 52 | 期: | 18 | 起(迄)頁: | 5649-5661 | 來源出版物: | Journal of Medicinal Chemistry | 摘要: | A novel series of topoisomerase I (Top I) inhibitors were designed on the basis of camptothecin using scaffold modification strategy. Thirty-one new compounds were synthesized and evaluated for anticell proliferation activity. The most potent compound 26 presented a significant inhibitory effect on Top I, leading to Top I-mediated cleavage and influences on Top I expression at the cellular level. Moreover, 26 was proved to induce cell death via apoptosis and accelerated DNA strand breaks without significant alteration in cell cycle populations. All of the experimental results herein indicated that 26 could interact with DNA-Top I complex and induce cancer cell apoptosis to produce antitumor effects. The in vivo evaluation of 26 on the growth of HT-29 tumor xenografts in nude mice suggested its therapeutic potential for further development. ? 2009 American Chemical Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-70349410539&doi=10.1021%2fjm900469e&partnerID=40&md5=8ad368048261f7fa055b0e73f18e99ef https://scholars.lib.ntu.edu.tw/handle/123456789/597285 |
ISSN: | 0022-2623 | DOI: | 10.1021/jm900469e | SDG/關鍵字: | 1 ethyl 3 (6 nitrobenzoxazol 2 yl) 6,8 difluoro 7 (3 methylpiperazin 1 yl) 4(1h) quinolone; antineoplastic agent; camptothecin; DNA; DNA topoisomerase inhibitor; naphthyridine derivative; quinolone derivative; scaffold protein; unclassified drug; animal experiment; animal tissue; antineoplastic activity; apoptosis; article; cancer cell culture; cancer cell destruction; cell cycle regulation; cell proliferation; cell strain HT29; cell viability; colony formation; controlled study; DNA content; DNA strand breakage; dose response; drug cytotoxicity; drug design; drug DNA binding; drug mechanism; drug screening; drug synthesis; enzyme inhibition; female; human; human cell; IC 50; mouse; nonhuman; nude mouse; protein cleavage; protein expression; structure activity relation; tumor xenograft; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; DNA; Drug Discovery; Enzyme Inhibitors; Female; Humans; Mice; Mice, Nude; Models, Molecular; Molecular Conformation; Naphthyridines; Neoplasms; Quinolones; Topoisomerase I Inhibitors; Transplantation, Heterologous |
顯示於: | 微生物學科所 |
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