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 CC 50 /IC 50 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 .