RESUMO
New 3-O-glycosyl-3-demethylthiocolchicines containing natural and unnatural sugar moieties were prepared and tested on gamma-aminobutyric acid (GABA) and strychnine-sensitive glycine receptors present in rat brain and spinal cord. Two different synthetic approaches were used with the readily available 3-O-demethylthiocolchicine (1b) and thiocolchicoside (2a). Glycosyl compounds 2a-g were obtained from 1b and 1-fluorosugars 4. 6'-Heterosubstituted glycosyl compounds 6-12 and the 6'-desoxy derivative 2h were prepared from 2a.
Assuntos
Colchicina/análogos & derivados , Colchicina/síntese química , Glicosídeos/síntese química , Receptores de GABA/metabolismo , Receptores de Glicina/metabolismo , Animais , Sítios de Ligação , Encéfalo/metabolismo , Colchicina/farmacologia , Glicosídeos/farmacologia , Técnicas In Vitro , Ligantes , Muscimol/farmacologia , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Relação Estrutura-Atividade , Estricnina/farmacologiaRESUMO
A novel class of 3-demethoxy-3-glycosylaminothiocolchicines (7) was prepared and tested for muscle relaxant activity. The syntheses were performed starting from the new 3-amino-3-demethoxythiocolchicine (5) prepared in good yield from 3-O-demethylthiocolchicine (1c) using the Buchwald-Hartwig reaction. The condensation of 5 with a series of pentose and hexose sugars (6) gave a series of 3-demethoxy-3-glycosylaminothiocolchicines (7). Their preparation was accomplished by adapting and improving a previous procedure for the preparation of N-arylglycosylamines. In particular, replacing traditional heating with microwave irradiation represents the key improvement of the process. The biological activity of the 3-demethoxy-3-glycosylaminothiocolchicines (7) was evaluated on GABA and strychnine-sensitive glycine receptors present in rat brain and spinal cord.