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Bioorg Med Chem ; 26(14): 4065-4072, 2018 08 07.
Article in English | MEDLINE | ID: mdl-30100019

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.


Subject(s)
Antiprotozoal Agents/pharmacology , Leishmania donovani/drug effects , Quinoxalines/pharmacology , Trypanosoma brucei brucei/drug effects , Trypanosoma cruzi/drug effects , Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/chemistry , Dose-Response Relationship, Drug , Molecular Structure , Parasitic Sensitivity Tests , Quinoxalines/chemical synthesis , Quinoxalines/chemistry , Structure-Activity Relationship
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