电邮这篇文章 Development of a New Inhibitor of Bacterial Cystathionine γ-Lyase Based on 6-Bromoindole and Aminothiophene
- 作者: Novikov R.A.1,2, Platonov D.N.2, Bely A.Y.2, Potapov K.V.1,2, Novikov M.A.1,2, Tomilov Y.V.2, Kechko O.I.1, Seregina T.A.1, Solyev P.N.1, Mitkevich V.A.1
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隶属关系:
- Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences
- Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
- 期: 卷 58, 编号 6 (2024)
- 页面: 975-982
- 栏目: ПОЛУЧЕНИЕ И СТРУКТУРНО-ФУНКЦИОНАЛЬНЫЙ АНАЛИЗ ПРОТИВОМИКРОБНЫХ СРЕДСТВ
- URL: https://innoscience.ru/0026-8984/article/view/677886
- DOI: https://doi.org/10.31857/S0026898424060083
- EDN: https://elibrary.ru/IAYTTU
- ID: 677886
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详细
Cystathionine γ-lyase (CSE) is a key enzyme for the H2S generation in such pathogenic bacteria as Staphylococcus aureus, Pseudomonas aeruginosa, etc. Suppression of CSE activity significantly increases the sensitivity of bacteria to the action of antibiotics. Here, we present a method for the synthesis of a novel indole-based CSE inhibitor, 3-amino-5-[(6-bromo-1H-indol-1-yl)methyl]thiophene, named MNS1. The synthesis of this compound is based on the modification of substituted thiophene as the main structural fragment, which is involved the alkylation of 6-bromoindole at the final stages. The dissociation constant of the MNS1 complex with bacterial CSE (from S. aureus, SaCSE) was 0.5 μM, which was an order of magnitude lower than that for human CSE (hCSE). The MNS1 compound was shown to effectively enhance the antibacterial effect of gentamicin against Bacillus subtilis, allowing it to be used as an antibiotic potentiator, to inhibit the growth of CSE-expressing bacterial cells.
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作者简介
R. Novikov
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences; Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991; Moscow, 119991
D. Platonov
Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991
A. Bely
Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991
K. Potapov
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences; Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991; Moscow, 119991
M. Novikov
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences; Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991; Moscow, 119991
Yu. Tomilov
Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991
O. Kechko
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991
T. Seregina
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991
P. Solyev
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences
编辑信件的主要联系方式.
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991
V. Mitkevich
Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences
Email: solyev@gmail.com
俄罗斯联邦, Moscow, 119991
参考
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