Novel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents : in vitro and in vivo evaluations
Background: Chagas disease is a life-threatening illness caused by Trypanosoma cruzi. The involvement of serine-/arginine-rich protein kinase in the T. cruzi life cycle is significant. Aims: To synthesize, characterize and evaluate the trypanocidal activity of diamides inspired by kinase inhibitor, SRPIN340. Material & Methods: Synthesis using a three-step process and characterization by infrared, nuclear magnetic resonance and high-resolution mass spectrometry were conducted. The selectivity index was obtained by the ratio of CC50/IC50 in two in vitro models. The most active compound, 3j, was evaluated using in vitro cytokine assays and assessing in vivo trypanocidal activity. Results: 3j activity in the macrophage J774 lineage showed an anti-inflammatory profile, and mice showed significantly reduced parasitemia and morbidity at low compound dosages. Conclusion: Novel diamide is active against T. cruzi in vitro and in vivo.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Future medicinal chemistry - 15(2023), 16 vom: 14. Aug., Seite 1469-1489 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vieira da Silva Torchelsen, Fernanda Karoline [VerfasserIn] |
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| Links: |
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| Themen: |
Chagas disease |
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| Anmerkungen: |
Date Revised 10.10.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.4155/fmc-2023-0090 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361485794 |
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| 100 | 1 | |a Vieira da Silva Torchelsen, Fernanda Karoline |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Novel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents |b in vitro and in vivo evaluations |
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| 500 | |a Citation Status Publisher | ||
| 520 | |a Background: Chagas disease is a life-threatening illness caused by Trypanosoma cruzi. The involvement of serine-/arginine-rich protein kinase in the T. cruzi life cycle is significant. Aims: To synthesize, characterize and evaluate the trypanocidal activity of diamides inspired by kinase inhibitor, SRPIN340. Material & Methods: Synthesis using a three-step process and characterization by infrared, nuclear magnetic resonance and high-resolution mass spectrometry were conducted. The selectivity index was obtained by the ratio of CC50/IC50 in two in vitro models. The most active compound, 3j, was evaluated using in vitro cytokine assays and assessing in vivo trypanocidal activity. Results: 3j activity in the macrophage J774 lineage showed an anti-inflammatory profile, and mice showed significantly reduced parasitemia and morbidity at low compound dosages. Conclusion: Novel diamide is active against T. cruzi in vitro and in vivo | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chagas disease | |
| 650 | 4 | |a SRPIN340 | |
| 650 | 4 | |a Trypanosoma cruzi | |
| 650 | 4 | |a diamides | |
| 650 | 4 | |a in vitro activity | |
| 650 | 4 | |a in vivo activity | |
| 700 | 1 | |a Fernandes Pedrosa, Tamiles Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Rodrigues, Michelle Peixoto |e verfasserin |4 aut | |
| 700 | 1 | |a de Aguiar, Alex Ramos |e verfasserin |4 aut | |
| 700 | 1 | |a de Oliveira, Fabrício Marques |e verfasserin |4 aut | |
| 700 | 1 | |a Amarante, Giovanni Wilson |e verfasserin |4 aut | |
| 700 | 1 | |a Sales-Junior, Policarpo Ademar |e verfasserin |4 aut | |
| 700 | 1 | |a Branquinho, Renata Tupinambá |e verfasserin |4 aut | |
| 700 | 1 | |a Gomes da Silva, Sirlaine Pio |e verfasserin |4 aut | |
| 700 | 1 | |a Talvani, André |e verfasserin |4 aut | |
| 700 | 1 | |a Fonseca Murta, Silvane Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Martins, Felipe Terra |e verfasserin |4 aut | |
| 700 | 1 | |a Braun, Rodrigo Ligabue |e verfasserin |4 aut | |
| 700 | 1 | |a Teixeira, Róbson Ricardo |e verfasserin |4 aut | |
| 700 | 1 | |a Furtado Mosqueira, Vanessa Carla |e verfasserin |4 aut | |
| 700 | 1 | |a Lana, Marta de |e verfasserin |4 aut | |
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