Discovery of novel Schistosoma mansoni PDE4A inhibitors as potential agents against schistosomiasis

Sebastián-Pérez, V. et al. (2019) Discovery of novel Schistosoma mansoni PDE4A inhibitors as potential agents against schistosomiasis. Future Medicinal Chemistry, 11(14), pp. 1703-1720. (doi: 10.4155/fmc-2018-0592) (PMID:31370708)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Munday, Dr Jane and De Koning, Professor Harry
Authors: Sebastián-Pérez, V., Schroeder, S., Munday, J.C., Van der Meer, T., Zaldívar-Díez, J., Siderius, M., De Koning, H. P., Brown, D.G., Martínez, A., Campillo, N.E., Leurs, R., and Gil, C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Future Medicinal Chemistry
Publisher:Future Science
ISSN (Online):1756-8927
Published Online:02 August 2019

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