Novel diamides inspired by protein kinase inhibitors as anti- Trypanosoma cruzi agents: in vitro and in vivo evaluations.

Future medicinal chemistry(2023)

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摘要
Chagas disease is a life-threatening illness caused by . The involvement of serine-arginine-rich protein kinase in the life cycle is significant. To synthesize, characterize and evaluate the trypanocidal activity of diamides inspired by kinase inhibitor, SRPIN340. 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 CC/IC in two models. The most active compound, , was evaluated using cytokine assays and assessing trypanocidal activity. activity in the macrophage J774 lineage showed an anti-inflammatory profile, and mice showed significantly reduced parasitemia and morbidity at low compound dosages. Novel diamide is active against and .
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关键词
Chagas disease, diamides, in vitro activity, in vivo activity, SRPIN340, Trypanosoma cruzi
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