Structure-activity relationships of novel N-imidazoylpiperazines with potent anti-trypanosoma cruzi activity.
CHÁVEZ, Rocio Marisol Espinoza; REZENDE JUNIOR, Celso de Oliveira; SOUZA, Mariana Laureano de; PAULI, Ivani; VALLI, Marilia; FERREIRA, Leonardo Luiz Gomes; CHELUCCI, Rafael Consolin; DUARTE, Simone Michelan; KROGH, Renata; SILVA, Fernando Bezerra Romualdo da; CRUZ, Fábio Cardoso; OLIVEIRA, Aldo Sena de; ANDRICOPULO, Adriano Defini; DIAS, Luiz Carlos.
CHÁVEZ, Rocio Marisol Espinoza; REZENDE JUNIOR, Celso de Oliveira; SOUZA, Mariana Laureano de; PAULI, Ivani; VALLI, Marilia; FERREIRA, Leonardo Luiz Gomes; CHELUCCI, Rafael Consolin; DUARTE, Simone Michelan; KROGH, Renata; SILVA, Fernando Bezerra Romualdo da; CRUZ, Fábio Cardoso; OLIVEIRA, Aldo Sena de; ANDRICOPULO, Adriano Defini; DIAS, Luiz Carlos.
Abstract: Chagas disease is caused by the parasite Trypanosoma cruzi, and the lack of effective and safe treatments makes identifying new classes of compounds with anti-T. cruzi activity of paramount importance. Methods: Hit-to-lead exploration of a metabolically stable N-imidazoylpiperazine was performed. Results: Compound 2, a piperazine derivative active against T. cruzi, was selected to perform the hit-to-lead exploration, which involved the design, synthesis and biological evaluation of 39 new derivatives. Conclusion: Compounds 6e and 10a were identified as optimized compounds with low micromolar in vitro activity, low cytotoxicity and suitable preliminary absorption, distribution, metabolism and excretion and physicochemical properties. Both compounds reduced parasitemia in mouse models of Chagas disease, providing a promising opportunity for further exploration of new antichagasic compounds.
@article={003182898,author = {CHÁVEZ, Rocio Marisol Espinoza; REZENDE JUNIOR, Celso de Oliveira; SOUZA, Mariana Laureano de; PAULI, Ivani; VALLI, Marilia; FERREIRA, Leonardo Luiz Gomes; CHELUCCI, Rafael Consolin; DUARTE, Simone Michelan; KROGH, Renata; SILVA, Fernando Bezerra Romualdo da; CRUZ, Fábio Cardoso; OLIVEIRA, Aldo Sena de; ANDRICOPULO, Adriano Defini; DIAS, Luiz Carlos.},title={Structure-activity relationships of novel N-imidazoylpiperazines with potent anti-trypanosoma cruzi activity},journal={Future Medicinal Chemistry},note={v. 16, n. 3, p. 253-269},year={2024}}