Novel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents: in vitro and in vivo evaluations.
Future Med Chem
; 15(16): 1469-1489, 2023 Aug.
Article
em En
| MEDLINE
| ID: mdl-37650735
ABSTRACT
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.
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MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article