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Relationship among structure, cytotoxicity, and Michael acceptor reactivity of quinocidin
http://hdl.handle.net/2237/00032335
http://hdl.handle.net/2237/00032335e2195336-b428-468d-a6a3-c21568ecd0a4
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
BMC_Nakagawa (709.0 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2020-06-10 | |||||
| タイトル | ||||||
| タイトル | Relationship among structure, cytotoxicity, and Michael acceptor reactivity of quinocidin | |||||
| 言語 | en | |||||
| 著者 |
Nakagawa, Yu
× Nakagawa, Yu× Sawaki, Yuki× Miyanishi, Wataru× Shimomura, Sayako× Shibata, Takahiro× Ojika, Makoto |
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| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | © 2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Antibiotic | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Anticancer | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Heterocycle | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Michael addition | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Structure–activity relationship | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Quinocidin (QCD) is a cytotoxic antibiotic with an unusual 3,4-dihydroquinolizinium skeleton. We previously found that QCD captures thiols in neutral aqueous media via a Michael addition-type reaction. However, it remains unclear whether the Michael acceptor reactivity of QCD is responsible for its cytotoxicity. In this study, we synthesized thirteen analogs of QCD to examine the relationship among its structure, cytotoxicity, and reactivity toward thiols. Thiol-trapping experiments and cytotoxicity tests collectively suggested that the Michael acceptor function of QCD is independent of its cytotoxic activity, and that the pyridinium moiety with the hydrophobic side chain is a key structural factor for cytotoxicity. These findings further led us to demonstrate that incorporation of an amide group into the side chain of QCD significantly reduced its toxicity but hardly affected the Michael acceptor function. The present study lays the foundation for QCD-based drug design and highlights the potential of QCD as a unique electrophile for use in the development of covalent inhibitors and protein-labeling probes. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | ファイル公開：2022-02-15 | |||||
| 言語 | ja | |||||
| 出版者 | ||||||
| 出版者 | Elsevier | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプresource | http://purl.org/coar/resource_type/c_6501 | |||||
| タイプ | journal article | |||||
| 出版タイプ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.bmc.2020.115308 | |||||
| ISSN（print） | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 0968-0896 | |||||
| 書誌情報 |
en : Bioorganic & Medicinal Chemistry 巻 28, 号 4, p. 115308, 発行日 2020-02-15 |
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| 著者版フラグ | ||||||
| 値 | author | |||||
