Preparation and biological activity of manno- and galacto-validamines, new 5a-carba-glycosylamines as alpha-glycosidase inhibitors.
Manno- and galacto-validamines, which are epimers of validamine, were semi-synthesized by the configurational inversion of validamine, a pseudo-sugar analogue of alpha-D-gluco-pyranose that has inhibitory activity for alpha-glucosidases. The inhibitory activities of these analogues were determined against several mannosidases and galactosidase. Manno-validamine shows potent inhibition for the alpha-mannosidases (competitive. K(i) = 4.6 x 10(-5) M for jack beans, and competitive, Ki = 2.8 x 10(-5) M for almonds), and galacto-validamine shows weak inhibition for the alpha-galactosidases (coffee bean and E. coli). The inhibitory effect of the epimers on the N-linked oligosaccharide-processing mannosidases involved in glycoprotein biosynthesis and lysosomal mannosidase from rat liver were also examined. Mannovalidamine shows potent inhibition on the endoplasmic reticulumal alpha-mannosidase (competitive, K(i) = 1.2 x 10(-6) M), Golgi mannosidases IA, II (competitive, K(i) = 2.8 x 10(-5) M), and lysosomal alpha-mannosidase (competitive, Ki = 1.7 x 10(-5) M).
Kameda
Y
Y
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa city, Japan.
Kawashima
K
K
Takeuchi
M
M
Ikeda
K
K
Asano
N
N
Matsui
K
K
D000818:Animals; D002240:Carbohydrate Sequence; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005688:Galactosamine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007294:Inositol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008969:Molecular Sequence Data; D051381:Rats
D004791:Enzyme Inhibitors; D007294:Inositol; D005688:Galactosamine; D006026:Glycoside Hydrolases