Deciphering the enzymatic target of a new family of antischistosomal agents bearing a quinazoline scaffold using complementary computational tools
A previous phenotypic screening campaign led to the identification of a quinazoline derivative with promising in vitro activity against Schistosoma mansoni. Follow-up studies of the antischistosomal potential of this candidate are presented here. The in vivo studies in a S. mansoni mouse model show a significant reduction of total worms and a complete disappearance of immature eggs when administered concomitantly with praziquantel in comparison with the administration of praziquantel alone. This fact is of utmost importance because eggs are responsible for the pathology and transmission of the disease. Subsequently, the chemical optimisation of the structure in order to improve the metabolic stability of the parent compound was carried out leading to derivatives with improved drug-like properties. Additionally, the putative target of this new class of antischistosomal compounds was envisaged by using computational tools and the binding mode to the target enzyme, aldose reductase, was proposed.
| 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: 07. Dez., Seite 511-523 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sebastian-Perez, Victor [VerfasserIn] |
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| Links: |
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| Themen: |
Aldehyde Reductase |
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| Anmerkungen: |
Date Completed 05.03.2020 Date Revised 07.05.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/14756366.2020.1712595 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM305378597 |
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| 245 | 1 | 0 | |a Deciphering the enzymatic target of a new family of antischistosomal agents bearing a quinazoline scaffold using complementary computational tools |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a A previous phenotypic screening campaign led to the identification of a quinazoline derivative with promising in vitro activity against Schistosoma mansoni. Follow-up studies of the antischistosomal potential of this candidate are presented here. The in vivo studies in a S. mansoni mouse model show a significant reduction of total worms and a complete disappearance of immature eggs when administered concomitantly with praziquantel in comparison with the administration of praziquantel alone. This fact is of utmost importance because eggs are responsible for the pathology and transmission of the disease. Subsequently, the chemical optimisation of the structure in order to improve the metabolic stability of the parent compound was carried out leading to derivatives with improved drug-like properties. Additionally, the putative target of this new class of antischistosomal compounds was envisaged by using computational tools and the binding mode to the target enzyme, aldose reductase, was proposed | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Drug discovery | |
| 650 | 4 | |a Schistosoma mansoni | |
| 650 | 4 | |a quinazoline | |
| 650 | 4 | |a target deconvolution | |
| 650 | 7 | |a Anthelmintics |2 NLM | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Quinazolines |2 NLM | |
| 650 | 7 | |a Aldehyde Reductase |2 NLM | |
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| 700 | 1 | |a García-Rubia, Alfonso |e verfasserin |4 aut | |
| 700 | 1 | |a Seif El-Din, Sayed H |e verfasserin |4 aut | |
| 700 | 1 | |a Sabra, Abdel-Nasser A |e verfasserin |4 aut | |
| 700 | 1 | |a El-Lakkany, Naglaa M |e verfasserin |4 aut | |
| 700 | 1 | |a William, Samia |e verfasserin |4 aut | |
| 700 | 1 | |a Blundell, Tom L |e verfasserin |4 aut | |
| 700 | 1 | |a Maes, Louis |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez, Ana |e verfasserin |4 aut | |
| 700 | 1 | |a Campillo, Nuria E |e verfasserin |4 aut | |
| 700 | 1 | |a Botros, Sanaa S |e verfasserin |4 aut | |
| 700 | 1 | |a Gil, Carmen |e verfasserin |4 aut | |
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