Structure–Activity Relationships of Novel N -Imidazoylpiperazines with Potent Anti- Trypanosoma Cruzi Activity

• DOI: 10.4155/fmc-2023-0185
• Publication Date: 2024-01-09T09:54:53Z
• Authors: Rocío Marisol Esp...; Celso de Oliveira...; Mariana Laureano ...; Ivani Pauli; Marilia Valli; Leonardo Luiz Gom...; Rafael Consolin C...; Simone Michelan-D...; Renata Krogh; Fernando Bezerra ...; Fábio Cardoso Cruz; Aldo Sena de Oliv...; Adriano Defini An...; Luiz Carlos Dias
• Keywords: Chagas Disease; Piperazine; Trypanocidal agent; Lead compound

Background: Chagas disease is caused by the parasite Trypanosoma cruzi, and lack of effective safe treatments makes identifying new classes compounds with anti-T. cruzi activity paramount importance. Methods: Hit-to-lead exploration a metabolically stable N-imidazoylpiperazine was performed. Results: Compound 2, piperazine derivative active against T. selected to perform hit-to-lead exploration, which involved design, synthesis biological evaluation 39 derivatives. Conclusion: Compounds 6e 10a were identified as optimized low micromolar in vitro activity, cytotoxicity suitable preliminary absorption, distribution, metabolism excretion physicochemical properties. Both reduced parasitemia mouse models disease, providing promising opportunity for further antichagasic compounds.