Towards discovery of new leishmanicidal scaffolds able to inhibit Leishmania GSK-3
Previous reports have validated the glycogen synthase kinase-3 (GSK-3) as a druggable target against the human protozoan parasite Leishmania. This prompted us to search for new leishmanicidal scaffolds as inhibitors of this enzyme from our in-house library of human GSK-3β inhibitors, as well as from the Leishbox collection of leishmanicidal compounds developed by GlaxoSmithKline. As a result, new leishmanicidal inhibitors acting on Leishmania GSK-3 at micromolar concentrations were found. These inhibitors belong to six different chemical classes (thiadiazolidindione, halomethylketone, maleimide, benzoimidazole, N-phenylpyrimidine-2-amine and oxadiazole). In addition, the binding mode of the most active compounds into Leishmania GSK-3 was approached using computational tools. On the whole, we have uncovered new chemical scaffolds with an appealing prospective in the development and use of Leishmania GSK-3 inhibitors against this infectious protozoan.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Journal of enzyme inhibition and medicinal chemistry - 35(2020), 1 vom: 02. Dez., Seite 199-210 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Martínez de Iturrate, Paula [VerfasserIn] |
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| Links: |
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| Themen: |
Antiprotozoal Agents |
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| Anmerkungen: |
Date Completed 13.01.2020 Date Revised 07.05.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/14756366.2019.1693704 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM303551836 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Previous reports have validated the glycogen synthase kinase-3 (GSK-3) as a druggable target against the human protozoan parasite Leishmania. This prompted us to search for new leishmanicidal scaffolds as inhibitors of this enzyme from our in-house library of human GSK-3β inhibitors, as well as from the Leishbox collection of leishmanicidal compounds developed by GlaxoSmithKline. As a result, new leishmanicidal inhibitors acting on Leishmania GSK-3 at micromolar concentrations were found. These inhibitors belong to six different chemical classes (thiadiazolidindione, halomethylketone, maleimide, benzoimidazole, N-phenylpyrimidine-2-amine and oxadiazole). In addition, the binding mode of the most active compounds into Leishmania GSK-3 was approached using computational tools. On the whole, we have uncovered new chemical scaffolds with an appealing prospective in the development and use of Leishmania GSK-3 inhibitors against this infectious protozoan | ||
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| 700 | 1 | |a Sebastián-Pérez, Victor |e verfasserin |4 aut | |
| 700 | 1 | |a Nácher-Vázquez, Montserrat |e verfasserin |4 aut | |
| 700 | 1 | |a Tremper, Catherine S |e verfasserin |4 aut | |
| 700 | 1 | |a Smirlis, Despina |e verfasserin |4 aut | |
| 700 | 1 | |a Martín, Julio |e verfasserin |4 aut | |
| 700 | 1 | |a Martínez, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Campillo, Nuria E |e verfasserin |4 aut | |
| 700 | 1 | |a Rivas, Luis |e verfasserin |4 aut | |
| 700 | 1 | |a Gil, Carmen |e verfasserin |4 aut | |
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