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 IC(50) 2.3 microM (1) and 3.7 microM (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 IC(50) 100 and 105 microM (Y strain), respectively, and 110 microM (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 IC(50) 10 and 200 microM against Y and Bolivia strains, respectively.
Bernardes
Lilian Sibelle Campos
LS
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, 14040-903 Ribeirão Preto-SP, Brazil.
Kato
Massuo Jorge
MJ
Albuquerque
Sérgio
S
Carvalho
Ivone
I
D000818:Animals; D002072:Butylene Glycols / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D017550:Spectroscopy, Fourier Transform Infrared; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
C515582:1,4-bis-(3,4,5-trimethoxy-phenyl)-1,4-butanediol; C515583:1,4-bis-(3,4-dimethoxyphenyl)-1,4-butanediol; D002072:Butylene Glycols; D014344:Trypanocidal Agents