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

Víctor Sebastián-Pérez, Susanne Schroeder, Jane C. Munday, Tiffany Van Der Meer, Josefa Zaldívar-Díez, Marco Siderius, Harry P. De Koning, Dave Brown, Ana Martínez, Nuria E. Campillo, Rob Leurs, Carmen Gil*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)1703-1720
Number of pages18
JournalFuture Medicinal Chemistry
Issue number14
Publication statusPublished - Jul 2019


The EC 7th Framework Programme (FP7-HEALTH-2013-INNOVATION-1, PDE4NPD no. 602666); RICET (RD16/0027/0010); FEDER funds and MECD (grant FPU15/1465 to Sebastián-Pérez and FPU13/00362 to Zaldívar-Díez) are acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

FundersFunder number
EC 7th Framework Programme
Seventh Framework Programme602666
Ministerio de Educación, Cultura y DeporteFPU13/00362, FPU15/1465
European Regional Development Fund


    • inhibitors
    • phosphodiesterase
    • schistosomiasis
    • virtual screening


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