| アイテムタイプ |
共通アイテムタイプ(1) |
| 公開日 |
2025-07-29 |
| タイトル |
|
|
タイトル |
Discovery of Antibacterial Compounds with Potential Multi-Pharmacology against Staphylococcus Mur ligase Family Members by In Silico Structure-Based Drug Screening |
|
言語 |
en |
| 著者 |
Teshima, Mio
Monobe, Kohei
Okubo, Saya
青木, 俊介
|
| 著作権関連情報 |
|
|
権利情報Resource |
https://creativecommons.org/licenses/by/4.0/ |
|
権利情報 |
Copyright (c) 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/). |
|
言語 |
en |
| 抄録 |
|
|
内容記述タイプ |
Abstract |
|
内容記述 |
Staphylococcus aureus (S. aureus) is a major bacterial infection in humans, leading to severe disease and causing death. The stagnation of antibiotic development in recent decades has made it difficult to combat drug-resistant infections. In this study, we performed an in silico structure-based drug screening (SBDS) targeting the S. aureus MurE (saMurE) enzyme involved in cell wall synthesis of S. aureus. saMurE is an enzyme that is essential for the survival of S. aureus but not present in humans. SBDS identified nine saMurE inhibitor candidates, Compounds 1–9, from a structural library of 154,118 compounds. Among them, Compound 2 showed strong antibacterial activity against Staphylococcus epidermidis (S. epidermidis) used as a model bacterium. Amino acid sequence homology between saMurE and S. epidermidis MurE is 87.4%, suggesting that Compound 2 has a similar inhibitory effect on S. aureus. Compound 2 showed an IC50 value of 301 nM for S. epidermidis in the dose-dependent growth inhibition assay. Molecular dynamics simulation showed that Compound 2 binds stably to both S. aureus MurD and S. aureus MurF, suggesting that it is a potential multi-pharmacological pharmacological inhibitor. The structural and bioactivity information of Compound 2, as well as its potential multiple-target activity, could contribute to developing new antimicrobial agents based on MurE inhibition. |
|
言語 |
en |
| 書誌情報 |
en : Macromolecules
巻 29,
号 16,
p. 3792,
発行日 2024-08-10
|
| 出版社 |
|
|
出版者 |
American Chemical Society |
|
言語 |
en |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
MurE |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
Staphylococcus aureus |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
in silico structure-based drug screening (SBDS) |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
docking simulation |
| キーワード |
|
|
言語 |
en |
|
主題Scheme |
Other |
|
主題 |
molecular dynamics simulation |
| 言語 |
|
|
言語 |
eng |
| 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 |
| 出版タイプ |
|
|
出版タイプ |
VoR |
|
出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| DOI |
|
|
|
識別子タイプ |
DOI |
|
|
関連識別子 |
https://doi.org/10.3390/molecules29163792 |
| NCID |
|
|
収録物識別子タイプ |
NCID |
|
収録物識別子 |
AA0071963X |
| ISSN |
|
|
収録物識別子タイプ |
PISSN |
|
収録物識別子 |
0024-9297 |
| ISSN |
|
|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
1520-5835 |
| 研究者情報 |
|
|
URL |
https://hyokadb02.jimu.kyutech.ac.jp/html/282_ja.html |
| 論文ID（連携） |
|
|
値 |
10461895 |
| 連携ID |
|
|
値 |
14732 |
10461895.pdf (1.7 MB)
