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Identification of Antischistosomal Leads by Evaluating Bridged 1,2,4,5-Tetraoxanes, Alphaperoxides, and Tricyclic Monoperoxidesстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 6 сентября 2017 г.
- Авторы: Ingram Katrin, Yaremenko Ivan A., Krylov Igor B., Hofer Lorenz, Terent'ev Alexander O., Keiser Jennifer
- Журнал: Journal of Medicinal Chemistry
- Том: 55
- Номер: 20
- Год издания: 2012
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 8700
- Последняя страница: 8711
- DOI: 10.1021/jm3009184
- Аннотация: Although antischistosomal properties of peroxides were studied in recent years, systematic structure activity relationships have not been conducted. We evaluated the antischistosomal potential of 64 peroxides belonging to bridged 1,2,4,5-tetraoxanes, alphaperoxides, and tricyclic monoperoxides. Thirty-nine compounds presented IC50 values <15 mu M on newly transformed schistosomula. Active drugs featured phenyl-, adamantane-, or alkyl residues at the methylene bridge. Lower susceptibility was documented on adult schistosomes, with most hit compounds being tricyclic monoperoxides (IC50: 7.7-13.4 mu M). A bridged 1,2,4,5-tetraoxane characterized by an adamantane residue showed the highest activity (IC50: 0.3 mu M) on adult Schistosoma mansoni. Studies with hemin and heme supplemented medium indicated that antischistosomal activation of peroxides is not necessarily triggered by iron porphyrins. Two compounds (tricyclic monoperoxide; bridged 1,2,4,5-tetraoxane) revealed high worm burden reductions in the chronic (WBR: 75.4-82.8%) but only moderate activity in the juvenile (WBR: 18.9-43.1%) S. mansoni mouse model. Our results might serve as suiting point for the preparation and evaluation of related derivatives.
- Добавил в систему: Ярёменко Иван Андреевич