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Lamellarin-inspired potent topoisomerase I inhibitors with the unprecedented benzo[g][1]benzopyrano[4,3-b]indol-6(13H)-one scaffold
http://hdl.handle.net/10069/38935
http://hdl.handle.net/10069/389350aa385cd-d0f1-44f0-bce7-e80a1757aaa9
名前 / ファイル | ライセンス | アクション |
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BMC27_265.pdf (1.5 MB)
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Supplementary_data.pdf (6.2 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2020-12-18 | |||||
タイトル | ||||||
タイトル | Lamellarin-inspired potent topoisomerase I inhibitors with the unprecedented benzo[g][1]benzopyrano[4,3-b]indol-6(13H)-one scaffold | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Topoisomerase I inhibitors | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Lamellarin D | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | BBPI | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Scaffold hopping | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Antitumor activity | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Fukuda, Tsutomu
× Fukuda, Tsutomu× Nanjo, Yusuke× Fujimoto, Masahiro× Yoshida, Kenyu× Natsui, Yuko× Ishibashi, Fumito× Okazaki, Fumiyasu× To, Hideto× Iwao, Masatomo |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | A new class of topoisomerase I inhibitors containing the unprecedented benzo[g][1]benzopyrano[4,3-b]indol-6(13H)-one (abbreviated as BBPI) ring system have been developed based on structure-activity relationship studies of the cytotoxic marine alkaloid lamellarin D. The pentacyclic BBPI scaffold was constructed from N-tert-butoxycarbonylpyrrole by sequential and regioselective functionalization of the pyrrole core using directed lithiation, conventional electrophilic substitution, and palladium-catalyzed cross-coupling reactions. Further N-alkylation of the scaffold followed by selective deprotection of the O-isopropyl group produced a range of N-substituted BBPI derivatives. The BBPIs thus prepared exhibited potent topoisomerase I inhibitory activity in DNA relaxation assays. The activities of BBPIs were higher than those of lamellarin D and camptothecin; they showed potent and selective antiproliferative activity in the panel of 39 human cancer cell lines established by Japanese Foundation for Cancer Research. COMPARE analyses indicated that the inhibition patterns of the BBPIs correlated well with those of the known topoisomerase I inhibitors such as SN-38 and TAS-103. The water-soluble valine ester derivative exhibited antitumor activity in vivo against murine colon carcinoma colon 26. The activity was comparable to that of the approved anticancer agent irinotecan. | |||||
書誌情報 |
Bioorganic & Medicinal Chemistry 巻 27, 号 2, p. 265-277, 発行日 2019-01-15 |
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出版者 | ||||||
出版者 | Elsevier Ltd. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 09680896 | |||||
DOI | ||||||
関連タイプ | isVersionOf | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1016/j.bmc.2018.11.037 | |||||
権利 | ||||||
権利情報 | c2018, Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
著者版フラグ | ||||||
出版タイプ | AM | |||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Bioorganic & Medicinal Chemistry, 27(2), pp.265-277; 2019 |