Quinoxaline derivatives as potential antitrypanosomal and antileishmanial agents

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry; v. 26, n. 14, p. 4065-4072, AUG 7 2018.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock
• Grantee: Arlene Gonçalves Corrêa
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/50680-8 - Quinoxaline derivatives as antiparasitic drugs: proof of concept
• Grantee: Arlene Gonçalves Corrêa
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE