RESUMO
Novel nucleoside analogues named "triazoxins" were synthesized. Of these, two analogues were found to be highly effective against Giardia lamblia, an intestinal parasite and a major cause of waterborne infection, worldwide. While compound 7 reduced the growth of trophozoites in culture (IC50, ~5 µM), compound 21 blocked the in vitro cyst production (IC50 ~5 µM). Compound 21 was also effective against trophozoites (IC50, ~36 µM). A third analogue (compound 8) was effective against both trophozoites (IC50, ~36 µM) and cysts (IC50, ~20 µM) although at higher concentration. Thus triazoxin analogues are unique and exhibit morphology (i.e., trohozoites or cysts) -specific effects against Giardia.
Assuntos
Anti-Infecciosos/síntese química , Giardia lamblia/efeitos dos fármacos , Giardíase/tratamento farmacológico , Nucleosídeos/síntese química , Anti-Infecciosos/farmacologia , Catálise , Desenho de Fármacos , Humanos , Imidazóis/química , Estrutura Molecular , Nucleosídeos/análogos & derivados , Nucleosídeos/farmacologia , Propanóis/química , Relação Estrutura-Atividade , Trofozoítos/efeitos dos fármacos , Uridina/químicaRESUMO
1,2-Diaryloxyethene has recently been proposed as a linker in singlet oxygen-mediated drug release. Even though 1,2-diaryloxyethenes look very simple, their synthesis was not an easy task. Previous methods are limited to symmetric molecules, lengthy step and low yield. We report on a facile synthetic method not only for 1,2-diaryloxyethenes but also their sulfur and nitrogen analogs in yields ranging from 40 to 90% with more than 90% purity at the vinylation reaction.