| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2023-11-20 |
| タイトル |
|
|
タイトル |
Cell-based screening of extracts of natural sources to search for inhibitors of the ubiquitin-proteasome system and identification of proteasome inhibitors from the fungus Remotididymella sp. |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| キーワード |
|
|
主題 |
The ubiquitin-proteasome system, Cell-based screening, Proteasome inhibitor, Remotididymella sp., Leptosphaerodione |
| 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 |
Soichiro, Nishimura
Yuki, Hitora
Teppei, Kawahara
Mika, Tanabe
Eisuke, Ogata
Hikaru, Kato
Pattaravadee, Srikoon
Takashi, Watanabe
塚本, 佐知子
|
| 内容記述 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
The ubiquitin-proteasome system (UPS) regulates selective protein degradation to maintain protein homeostasis. Small molecules that inhibit the UPS-dependent protein degradation are promising anti-tumor agents. We report a cell-based luminescent assay using HeLa cells expressing luciferase-fused oxygen-dependent destruction domain (ODD) of hypoxia-inducible factor 1 α (HIF-1 α). ODD is degraded by the UPS and this assay system can aid in the identification of natural products that inhibit either process of the UPS, including ubiquitination/deubiquitination and proteasomal degradation. This reporter assay can exclude the influences of coloring or fluorescent compounds in extracts, thereby leading to effective high-throughput processing. The screening of 15,025 extracts of natural sources identified the culture extract of the fungus Remotididymella sp. (18F02908). Bioassay-guided isolation yielded two new polyketides, mellains A (1) and B (2), together with leptosphaerodione (3) and its acetone adduct 4. Compound 1 was revealed to have an unprecedented benzo[g]isoquinoline-8,10-dione skeleton. Evaluation of the biological activities demonstrated that these polyketides inhibit the proteasomal proteolysis. This is the first report of the identification of proteasome inhibitors from natural sources using a cell-based reporter assay targeting UPS inhibitors. |
| 書誌情報 |
en : Bioorganic & Medicinal Chemistry Letters
巻 59,
p. 128566,
発行年 2022-03-01
|
| ISSN |
|
|
収録物識別子 |
0960-894X |
| DOI |
|
|
関連タイプ |
isVersionOf |
|
|
関連識別子 |
https://doi.org/10.1016/j.bmcl.2022.128566 |
| 権利 |
|
|
権利情報 |
(C)2022 Elsevier Ltd. All rights reserved. |
| 権利 |
|
|
権利情報 |
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 |
| 出版者 |
|
|
出版者 |
Elsevier |
j_bmcl_2022_128566.pdf (628 KB)
.png)
