Novel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents: in vitro and in vivo evaluations
Nenhuma Miniatura disponível
Data
2023-08-31
Autores
Título da Revista
ISSN da Revista
Título de Volume
Editor
Resumo
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. cruziin vitro and in vivo.
Descrição
Palavras-chave
Chagas disease, Diamides, In vitro activity, In vivo activity, SRPIN340, Trypanosoma cruzi
Citação
TORCHELSEN, Fernanda Karoline Vieira da Silva et al. Novel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents: in vitro and in vivo evaluations. Future Medicinal Chemistry, London, v. 15, n. 16, p. 1469-1489, 2023. DOI: 10.4155/fmc-2023-0090. Disponível em: https://www.future-science.com/doi/10.4155/fmc-2023-0090. Acesso em: 6 nov. 2023.