Discovery of Novel Schistosoma mansoni PDE4A Inhibitors as Potential Agents Against Schistosomiasis
作者： Víctor Sebastián-Pérez , Susanne Schroeder , Jane C Munday , Tiffany van der Meer , Josefa Zaldívar-Díez
关键词: Molecular mechanism 、 Schistosomiasis 、 Enzyme structure 、 Cyclic nucleotide phosphodiesterase 、 Chemical library 、 Phosphodiesterase 、 Biology 、 Computational biology 、 Virtual screening 、 Schistosoma mansoni
摘要: Aim: Due to the urgent need for effective drugs treat schistosomiasis that act through a known molecular mechanism of action, we focused on target-based approach with aim discover inhibitors cyclic nucleotide phosphodiesterase from Schistosoma mansoni (SmPDE4A). Materials & methods: To new SmPDE4A homology models enzyme structure were constructed based human and protozoan homologs. The best two selected subsequent virtual screening our in-house chemical library. Results conclusion: A total 25 library compounds experimental confirmation as after dose-response experiments, three top hits identified. results presented validate identify clinically relevant phosphodiesterases.
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