| アイテムタイプ |
学術雑誌論文 = Journal Article(1) |
| 公開日 |
2024-05-09 |
| 資源タイプ |
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|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
|
資源タイプ |
journal article |
| タイトル |
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|
タイトル |
Identification of Novel Antimicrobial Compounds Targeting Mycobacterium tuberculosis S-Adenosyl-L-Homocysteine Hydrolase Using Dual Hierarchical In Silico Structure-Based Drug Screening |
|
言語 |
en |
| 言語 |
|
|
言語 |
eng |
| 著者 |
Ito, Hazuki
Monobe, Kohei
Okubo, Saya
青木, 俊介
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| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
The emergence of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis (M. tuberculosis) has become a major medical problem. S-adenosyl-L-homocysteine hydrolase (MtSAHH) was selected as the target protein for the identification of novel anti-TB drugs. Dual hierarchical in silico Structure-Based Drug Screening was performed using a 3D compound structure library (with over 150 thousand synthetic chemicals) to identify compounds that bind to MtSAHH’s active site. In vitro experiments were conducted to verify whether the nine compounds selected as new drug candidates exhibited growth-inhibitory effects against mycobacteria. Eight of the nine compounds that were predicted by dual hierarchical screening showed growth-inhibitory effects against Mycobacterium smegmatis (M. smegmatis), a model organism for M. tuberculosis. Compound 7 showed the strongest antibacterial activity, with an IC50 value of 30.2 µM. Compound 7 did not inhibit the growth of Gram-negative bacteria or exert toxic effects on human cells. Molecular dynamics simulations of 40 ns using the MtSAHH–Compound 7 complex structure suggested that Compound 7 interacts stably with the MtSAHH active site. These in silico and in vitro results suggested that Compound 7 is a promising lead compound for the development of new anti-TB drugs. |
|
言語 |
en |
| 書誌情報 |
en : Molecules
巻 29,
号 6,
p. 1303,
発行日 2024-03-14
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| 出版社 |
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出版者 |
MDPI |
| DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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|
関連識別子 |
https://doi.org/10.3390/molecules29061303 |
| ISSN |
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収録物識別子タイプ |
EISSN |
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収録物識別子 |
1420-3049 |
| 著作権関連情報 |
|
|
権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
|
権利情報 |
Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
tuberculosis |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
Mycobacterium |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
Mycobacterium tuberculosis S-adenosyl-L-homocysteine hydrolase (MtSAHH) |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
in silico structure-based drug screening (SBDS) |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
docking simulation |
| キーワード |
|
|
主題Scheme |
Other |
|
主題 |
molecular dynamics simulation |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 査読の有無 |
|
|
値 |
yes |
| 研究者情報 |
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|
URL |
https://hyokadb02.jimu.kyutech.ac.jp/html/282_ja.html |
| 論文ID（連携） |
|
|
値 |
10430118 |
| 連携ID |
|
|
値 |
12173 |
10430118.pdf (4.2 MB)
