2. Academic Validation
  3. Quinoxaline derivatives as potential antitrypanosomal and antileishmanial agents

Quinoxaline derivatives as potential antitrypanosomal and antileishmanial agents

  • Bioorg Med Chem. 2018 Aug 7;26(14):4065-4072. doi: 10.1016/j.bmc.2018.06.033.
Juliana Cogo 1,  Juan Cantizani 2,  Ignacio Cotillo 2,  Diego Pereira Sangi 3,  Arlene Gonçalves Corrêa 4,  Tânia Ueda-Nakamura 1,  Benedito Prado Dias Filho 1,  José Julio Martín 2,  Celso Vataru Nakamura 5
Affiliations

Affiliations

  • 1 Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Avenida Colombo 5790, 87020-900 Maringá, PR, Brazil.
  • 2 Diseases of the Developing World (DDW), Tres Cantos Medicines Development Campus, GlaxoSmithKline, Tres Cantos, Spain.
  • 3 Laboratório de Síntese de Produtos Naturais, Departamento de Química, Universidade Federal de São Carlos, Rodovia Washington Luis km 235, 13565-905 São Carlos, SP, Brazil; Instituto de Ciências Exatas, Universidade Federal Fluminense, 27213-145 Volta Redonda, RJ, Brazil.
  • 4 Laboratório de Síntese de Produtos Naturais, Departamento de Química, Universidade Federal de São Carlos, Rodovia Washington Luis km 235, 13565-905 São Carlos, SP, Brazil. Electronic address: agcorrea@ufscar.br.
  • 5 Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Estadual de Maringá, Avenida Colombo 5790, 87020-900 Maringá, PR, Brazil. Electronic address: cvnakamura@uem.br.
PMID: 30100019 DOI: 10.1016/j.bmc.2018.06.033
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-diaryl-substituted 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.

Keywords

Leishmania donovani; Quinoxaline derivatives; Trypanosoma brucei; Trypanosoma cruzi.

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