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Semisynthetic Amides of Amphotericin B and Nystatin A1: A Comparative Study of In Vitro Activity/Toxicity Ratio in Relation to Selectivity to Ergosterol Membranesстатья
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: Tevyashova Anna, Efimova Svetlana, Alexandrov Alexander, Omelchuk Olga, Ghazy Eslam, Bychkova Elena, Zatonsky Georgy, Grammatikova Natalia, Dezhenkova Lyubov, Solovieva Svetlana, Ostroumova Olga, Shchekotikhin Andrey
- Журнал: Antibiotics
- Том: 12
- Номер: 1
- Год издания: 2023
- Издательство: MDPI Publishing
- Местоположение издательства: Basel, Switzerland, Switzerland
- Первая страница: 151
- Последняя страница: 151
- DOI: 10.3390/antibiotics12010151
- Аннотация: Polyene antifungal amphotericin B (AmB) has been used for over 60 years, and remains a valuable clinical treatment for systemic mycoses, due to its broad antifungal activity and low rate of emerging resistance. There is no consensus on how exactly it kills fungal cells but it is certain that AmB and the closely-related nystatin (Nys) can form pores in membranes and have a higher affinity towards ergosterol than cholesterol. Notably, the high nephro- and hemolytic toxicity of polyenes and their low solubility in water have led to efforts to improve their properties. We present the synthesis of new amphotericin and nystatin amides and a comparative study of the effects of identical modifications of AmB and Nys on the relationship between their structure and properties. Generally, increases in the activity/toxicity ratio were in good agreement with increasing ratios of selective permeabilization of ergosterol- vs. cholesterol-containing membranes. We also show that the introduced modifications had an effect on the sensitivity of mutant yeast strains with alterations in ergosterol biosynthesis to the studied polyenes, suggesting a varying affinity towards intermediate ergosterol precursors. Three new water-soluble nystatin derivatives showed a prominent improvement in safety and were selected as promising candidates for drug development.
- Добавил в систему: Щекотихин Андрей Егорович