Discovery of novelSchistosoma mansoniPDE4A 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
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 fromSchistosoma 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. Aim: Schistosoma mansoni Materials & methods: Results & conclusion: Graphical abstract.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Future medicinal chemistry - 11(2019), 14, Seite 1703- |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sebastián-Pérez, Víctor [VerfasserIn] |
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| Links: |
FID Access [lizenzpflichtig] |
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| Umfang: |
1 Online-Ressource (18 p) |
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| doi: |
10.4155/fmc-2018-0592 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a 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 fromSchistosoma 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. Aim: Schistosoma mansoni Materials & methods: Results & conclusion: Graphical abstract | ||
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| 700 | 1 | |a Zaldívar-Díez, Josefa |e verfasserin |4 aut | |
| 700 | 1 | |a Siderius, Marco |e verfasserin |4 aut | |
| 700 | 1 | |a de Koning, Harry P |e verfasserin |4 aut | |
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| 700 | 1 | |a Leurs, Rob |e verfasserin |4 aut | |
| 700 | 1 | |a Gil, Carmen |e verfasserin |4 aut | |
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