Quinoxaline derivatives as potential antitrypanosomal and antileishmanial agents

Autor(es)

Cogo, Juliana ^[1] ; Cantizani, Juan ^[2] ; Cotillo, Ignacio ^[2] ; Sangi, Diego Pereira ^{[3, 4]} ; Correa, Arlene Goncalves ^[4] ; Ueda-Nakamura, Tania ^[1] ; Dias Filho, Benedito Prado ^[1] ; Julio Martin, Jose ^[2] ; Nakamura, Celso Vataru ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Maringa, Programa Posgrad Ciencias Farmaceut, Ave Colombo 5790, BR-87020900 Maringa, PR - Brazil

^[2] GlaxoSmithKline, DDW, Tres Cantos Med Dev Campus, Tres Cantos - Spain

^[3] Univ Fed Fluminense, Inst Ciencias Exatas, BR-27213145 Volta Redonda, RJ - Brazil

^[4] Univ Fed Sao Carlos, Dept Quim, Lab Sintese Prod Nat, Rodovia Washington Luis Km 235, BR-13565905 Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Bioorganic & Medicinal Chemistry; v. 26, n. 14, p. 4065-4072, AUG 7 2018.
• Citações Web of Science: 0

Resumo

Continuous efforts have been made to discover new drugs for the treatment of Chagas' disease, human African trypanosomiasis, and leishmaniasis. We have previously reported the synthesis and antileishmanial and antitrypanosomal (Y strain) properties of 2,3-disubstituted quinoxalines. Considering their promising antiparasitic potential, the present study was conducted to expand our search and take advantage of high-throughput assays to investigate the effects of quinoxaline derivatives against Leishmania donovani, Trypanosoma brucei, and Trypanosoma cruzi (Tulahuen strain). These compounds were active against the kinetoplastid parasites that were evaluated. The 2-chloro-3-methylsulfoxylsulfonyl and 2-chloro-3-methylsulfinyl quinoxalines were the most potent, and some of these derivatives were even more active than the reference drugs. Although the 2,3-diarylsubstituted quinoxalines were not active against all of the parasites, they were active against T. brucei and intracellular amastigotes of T. cruzi, without interfering with mammalian cell viability. These compounds presented encouraging results that will guide our future studies on in vivo bioassays towards the mode of action. (AU)

• Processo FAPESP: 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock
• Beneficiário: Arlene Gonçalves Corrêa
• Modalidade de apoio: Auxílio à Pesquisa - Programa Centros de Pesquisa em Engenharia
• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 13/50680-8 - Derivados de quinoxalinas como fármacos antiparasitários: prova de conceito
• Beneficiário: Arlene Gonçalves Corrêa
• Modalidade de apoio: Auxílio à Pesquisa - Parceria para Inovação Tecnológica - PITE