RESUMO
First synthesis of novel coumarin-trioxane hybrids is reported. The synthesis was achieved via condensation of ß-hydroxyhydroperoxides with coumarinic-aldehydes in presence of p-toluenesulfonic acid in good yields and the novel hybrids were evaluated for their antimalarial activity both in vitro and in vivo.
Assuntos
Antimaláricos/síntese química , Cumarínicos/química , Compostos Heterocíclicos/química , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Plasmodium yoelii/efeitos dos fármacos , Aldeídos/química , Animais , Antimaláricos/farmacologia , Benzenossulfonatos/química , Cumarínicos/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Compostos Heterocíclicos/farmacologia , Humanos , Concentração Inibidora 50 , Malária Falciparum/parasitologia , Camundongos , Peróxidos/química , Plasmodium falciparum/parasitologia , Plasmodium yoelii/parasitologia , Relação Estrutura-AtividadeRESUMO
An efficient conversion of artemisinin 1 into three new amino- and hydroxy-functionalized 11-aza prototypes 9, 11, and 12 has been achieved on a multigram scale by reaction with hydrazine, hydroxylamine, and 2-amino ethanol, respectively. Of these, 9 has been further diversified into a wide range of derivatives including imines, amines, amides, and linker based dimers. Prototypes 11 and 12 have been converted into the corresponding ethers in high yields. Some of these compounds have shown a high order of activity against multidrug-resistant malaria in mice by oral route.
