Future medicinal chemistry · 2019
Discovery of novel Schistosoma mansoni PDE4A inhibitors as potential agents against schistosomiasis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Sebastián-Pérez Víctor, Schroeder Susanne, Munday Jane C, van der Meer Tiffany, Zaldívar-Díez Josefa, Siderius Marco, de Koning Harry P, Brown Dave, Martínez Ana, Campillo Nuria E, Leurs Rob, Gil Carmen
Аннотация
Aim: Due to the urgent need for effective drugs to treat schistosomiasis that act through a known molecular mechanism of action, we focused on a target-based approach with the aim to discover inhibitors of a cyclic nucleotide phosphodiesterase from Schistosoma mansoni (SmPDE4A). Materials & methods: To discover new inhibitors of SmPDE4A homology models of the enzyme structure were constructed based on known human and protozoan homologs. The best two models were selected for subsequent virtual screening of our in-house chemical library. Results & conclusion: A total of 25 library compounds were selected for experimental confirmation as SmPDE4A inhibitors and after dose-response experiments, three top hits were identified. The results presented validate the virtual screening approach to identify new inhibitors for clinically relevant phosphodiesterases.