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Naphthyl-Substituted Indole and Pyrrole Carboxylic Acids as Effective Antibiotic Potentiators—Inhibitors of Bacterial Cystathionine γ-Lyaseстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 15 февраля 2024 г.
- Авторы: Kuzovlev A.S., Zybalov M.D., Golovin A.V., Biryukov M.V., Belik A.R., Silonov S.A., Yunin M.A., Ivanov R.A.
- Журнал: International Journal of Molecular Sciences
- Номер: 24
- Год издания: 2023
- Издательство: MDPI
- Местоположение издательства: Basel, Switzerland
- Номер статьи: 16331
- DOI: 10.3390/ijms242216331
- Аннотация: Over the past decades, the problem of bacterial resistance to most antibiotics has become a serious threat to patients’ survival. Nevertheless, antibiotics of a novel class have not been approved since the 1980s. The development of antibiotic potentiators is an appealing alternative to the challenging process of searching for new antimicrobials. Production of H2S—one of the leading defense mechanisms crucial for bacterial survival—can be influenced by the inhibition of relevant enzymes: bacterial cystathionine γ-lyase (bCSE), bacterial cystathionine β-synthase (bCBS), or 3-mercaptopyruvate sulfurtransferase (MST). The first one makes the main contribution to H2S generation. Herein, we present data on the synthesis, in silico analyses, and enzymatic and microbiological assays of novel bCSE inhibitors. Combined molecular docking and molecular dynamics analyses revealed a novel binding mode of these ligands to bCSE. Lead compound 2a manifested strong potentiating activity when applied in combination with some commonly used antibiotics against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. The compound was found to have favorable in vitro absorption, distribution, metabolism, excretion, and toxicity parameters. The high effectiveness and safety of compound 2a makes it a promising candidate for enhancing the activity of antibiotics against high-priority pathogens.
- Добавил в систему: Бирюков Михаил Владимирович
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