Synthesis and in vitro evaluation of novel galactosyl-triazolo-benzenesulfonamides against Trypanosoma cruzi

Journal of the Brazilian Chemical Society

Getúlio G. Junqueira²  Marcelo R. Carvalho²  Peterson De Andrade²  Carla D. Lopes¹  Zumira A. Carneiro¹  Renata Sesti-costa¹  João S. Silva¹  Ivone Carvalho² 

[1] ,Universidade de São Paulo Faculdade de Ciências Farmacêuticas de Ribeirão Preto Ribeirão Preto SP ,Brazil

关键词: Chagas disease;    Trypanosoma cruzi;    trans-sialidase;    benzenesulfonamides;    click chemistry;   

DOI  :  10.5935/0103-5053.20140158

来源: SciELO

【 摘 要 】

The only drugs approved for the treatment of Chagas disease, nifurtimox and benznidazole, present toxic side effects and limited efficacy in the chronic stage of the disease, which highlight the need for new drugs. Amongst the different molecular drug targets discovered in the parasite, Trypanosoma cruzi trans-sialidase (TcTS) has been considered crucial in the recognition and invasion of host cells. Hence, we report the efficient synthesis and biological evaluation (TcTS inhibition and antitrypanosomal activities) of some galactose-containing triazol-arylsulfonamides via microwave-assisted Cu(I) 1,3-dipolar azide-alkyne cycloaddition (CuAAC) based on azide benzenesulfonamides and a galactose-derived alkyne as precursors. Most of the compounds tested against TcTS showed moderate to weak inhibition (40%-15%), except one of the compounds (81%). Regarding the antitrypanosomal assay, some compounds [(IC50 70.9 µM) and (IC50 44.0 µM)] exhibited the most significant activities, although not as active as benznidazole (IC50 1.4 µM). Nevertheless, the cytotoxicity assessment showed that all compounds were not cytotoxic. In this preliminary work, we considered some compounds as lead scaffolds for further optimization.

【 授权许可】

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