Detalle de: Discovery of novel Schistosoma mansoni PDE4A inhibitors as potential agents against schistosomiasis
| Title | Discovery of novel Schistosoma mansoni PDE4A inhibitors as potential agents against schistosomiasis |
| Abstract |
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. |
| Apa Reference | Sebastián-Pérez, V., Schroeder, S., Munday, J. C., van der Meer, T., Zaldívar-Díez, J., Siderius, M., de Koning, H. P., Brown, D., Martínez, A., Campillo, N. E., Leurs, R., & Gil, C. (2019). Discovery of NovelSchistosoma MansoniPDE4A Inhibitors as Potential Agents against Schistosomiasis. Future Medicinal Chemistry, 11(14), 1703–1720. 10.4155/fmc-2018-0592 |
| Doi | 10.4155/FMC-2018-0592 |
| Publication Date | Jul 2019 |
| Publication Type | Article |
| Researcher | Ana Martínez |
| Ontology | Structural bioinformatics, Structure-function relationship, Drug Discovery and design, Structure prediction, Molecular Interactions/Docking |
| Research Groups | Translational Medicinal and Biological Chemistry |
| Tools |