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

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

Year of Publication: 2019
Contained in: Future medicinal chemistry Vol. 11, No. 14 (2019), p. 1703-1720
All journal articles: Search for all articles in this journal
Language: English
Contributors: Sebastián-Pérez, Víctor | Author
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
Full text access:
Electronic availability is being checked...
Links: Full Text (dx.doi.org)
Keywords: Journal Article
inhibitors
phosphodiesterase
schistosomiasis
virtual screening
ISSN: 1756-8927
Note: Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Notes: Date Revised 10.09.2019
published: Print-Electronic
Citation Status In-Data-Review
Copyright: From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Physical Description: Online-Ressource
ID (e.g. DOI, URN): 10.4155/fmc-2018-0592
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