2023-11-102023-11-102023-08-31TORCHELSEN, 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. DisponÃvel em: https://www.future-science.com/doi/10.4155/fmc-2023-0090. Acesso em: 6 nov. 2023.1756-8919e- 1756-8927https://www.future-science.com/doi/10.4155/fmc-2023-0090Background: 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.engAcesso RestritoChagas diseaseDiamidesIn vitro activityIn vivo activitySRPIN340Trypanosoma cruziNovel diamides inspired by protein kinase inhibitors as anti-Trypanosoma cruzi agents: in vitro and in vivo evaluationsArtigo10.4155/fmc-2023-0090