1,2,3-Triazole-based analogue of benznidazole displays remarkable activity against Trypanosoma cruzi.
作者： Peterson de Andrade , Oswaldo A. Galo , Marcelo R. Carvalho , Carla D. Lopes , Zumira A. Carneiro
DOI: 10.1016/J.BMC.2015.10.008
关键词: Trypanosoma cruzi 、 Cycloaddition 、 Chemistry 、 Stereochemistry 、 Click chemistry 、 1,2,3-Triazole 、 Nifurtimox 、 Cytotoxicity 、 Benznidazole 、 Chagas disease
摘要: Abstract The current treatment of Chagas disease is based on the use two drugs, nifurtimox and benznidazole, which present limited efficacy in chronic stage toxic side effects. Although some progress has been made development new drugs to treat this disease, discovery novel compounds urgently required. In work we report synthesis biological evaluation 1,2,3-triazole-based analogues benznidazole. A small series 27 was successfully synthesized via microwave-assisted copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) ruthenium-catalyzed (RuAAC) from N-benzyl-2-azidoacetamide (1) a set commercial terminal alkynes. Analogues 24 (IC50 40 μM) 28 50 μM) showed comparable activities benznidazole 34 μM) against trypomastigote form analogue 15 7 μM) found be most active. Regarding cytotoxicity assessment series, were not cytotoxic. This shows that designed strategy efficiently capable generating benzindazole reveals one more active than
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