Structure-activity relationships of novel N-imidazoylpiperazines with potent anti-Trypanosoma cruzi activity
Background: Chagas disease is caused by the parasite Trypanosoma cruzi, and the lack of effective and safe treatments makes identifying new classes of compounds with anti-T. cruzi activity of paramount importance. Methods: Hit-to-lead exploration of a metabolically stable N-imidazoylpiperazine was performed. Results: Compound 2, a piperazine derivative active against T. cruzi, was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives. Conclusion: Compounds 6e and 10a were identified as optimized compounds with low micromolar in vitro activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Future medicinal chemistry - 16(2024), 3 vom: 29. Jan., Seite 253-269 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Espinoza-Chávez, Rocío Marisol [VerfasserIn] |
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| Links: |
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| Themen: |
Chagas disease |
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| Anmerkungen: |
Date Completed 30.01.2024 Date Revised 30.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0185 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366839012 |
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| 520 | |a Background: Chagas disease is caused by the parasite Trypanosoma cruzi, and the lack of effective and safe treatments makes identifying new classes of compounds with anti-T. cruzi activity of paramount importance. Methods: Hit-to-lead exploration of a metabolically stable N-imidazoylpiperazine was performed. Results: Compound 2, a piperazine derivative active against T. cruzi, was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives. Conclusion: Compounds 6e and 10a were identified as optimized compounds with low micromolar in vitro activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a N-imidazoylpiperazines | |
| 650 | 4 | |a SAR | |
| 650 | 4 | |a Trypanosoma cruzi | |
| 650 | 4 | |a drug discovery | |
| 650 | 4 | |a hit-to-lead | |
| 650 | 7 | |a Trypanocidal Agents |2 NLM | |
| 700 | 1 | |a Oliveira Rezende Júnior, Celso de |e verfasserin |4 aut | |
| 700 | 1 | |a de Souza, Mariana Laureano |e verfasserin |4 aut | |
| 700 | 1 | |a Pauli, Ivani |e verfasserin |4 aut | |
| 700 | 1 | |a Valli, Marilia |e verfasserin |4 aut | |
| 700 | 1 | |a Gomes Ferreira, Leonardo Luiz |e verfasserin |4 aut | |
| 700 | 1 | |a Chelucci, Rafael Consolin |e verfasserin |4 aut | |
| 700 | 1 | |a Michelan-Duarte, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Krogh, Renata |e verfasserin |4 aut | |
| 700 | 1 | |a Romualdo da Silva, Fernando Bezerra |e verfasserin |4 aut | |
| 700 | 1 | |a Cruz, Fábio Cardoso |e verfasserin |4 aut | |
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| 700 | 1 | |a Andricopulo, Adriano Defini |e verfasserin |4 aut | |
| 700 | 1 | |a Dias, Luiz Carlos |e verfasserin |4 aut | |
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