Synthesis and trypanocidal activity of 1,4-bis-(3,4,5-trimethoxy-phenyl)-1,4-butanediol and 1,4-bis-(3,4-dimethoxyphenyl)-1,4-butanediol

Chagas’ disease is endemic in Central and South American countries. Specific chemotherapy with nifurtimox or benznidazole has been recommended for treatment of recent infection but they have limited efficacy. The natural products veraguensin (1) and grandisin (2) have shown potent in vitro activity against trypomastigote parasite (Y strain) with IC50 2.3 μM (1) and 3.7 μM (2). We report herein the synthesis and in vitro trypanocidal evaluation of symmetrical and unsymmetrical 1,4-diaryl-1,4-diol derivatives as potential trypanocidal analogs of natural compounds 1 and 2. Among the synthesized products, compounds 1,4-bis-(3,4,5-trimethoxyphenyl)-1,4-butanediol (6a) and 1,4-bis-(3,4-dimethoxyphenyl)-1,4-butanediol (6b) showed better activity against Trypanosoma cruzi trypomastigotes with IC50 100 and 105 μM (Y strain), respectively, and 110 μM (Bolivia strain) for both compounds. However, the most active compound of this series was 1,4-bis-(3,4-dimethoxyphenyl)butane-1,4-dione (7b) with IC50 10 and 200 μM against Y and Bolivia strains, respectively.

Two potential trypanocidal compounds 1,4-bis-(3,4,5-trimethoxyphenyl)-1,4-butanediol and 1,4-bis-(3,4-dimethoxyphenyl)-1,4-butanediol, prepared from 1,4-diaryl-1,4-diketones and 1,4-diarylacetylenic-1,4-glycols, are described.Figure optionsDownload as PowerPoint slide