Homonojirimycin analogues and their glucosides from Lobelia sessilifolia and Adenophora spp. (Campanulaceae).
2,6-Dideoxy-7-O-(beta-D-glucopyranosyl) 2,6-imino-D-glycero-L-gulo- heptitol (7-O-beta-D-glucopyranosyl-alpha-homonojirimycin, 1) was isolated from the 50% methanol extract of the whole plant of Lobelia sessilifolia (Campanulaceae), which was found to potently inhibit rice alpha-glucosidase. Adenophorae radix, roots of Adenophora spp. (Campanulaceae), yielded new homonojirimycin derivatives, adenophorine (2), 1-deoxyadenophorine (3), 5-deoxyadenophorine (4), 1-C-(5-amino-5-deoxy-beta-D-galactopyranosyl)butane (beta-1-C-butyl-deoxygalactonojirimycin, 5), and the 1-O-beta-D-glucosides of 2 (6) and 4 (7), in addition to the recently discovered alpha-1-C-ethylfagomine (8) and the known 1-deoxymannojirimycin (9) and 2R,5R-bis(hydroxymethyl)-3R,4R- dihydroxypyrrolidine (DMDP, 10). Compound 4 is a potent inhibitor of coffee bean alpha-galactosidase (IC50 = 6.4 microM) and a reasonably good inhibitor of bovine liver beta-galactosidase (IC50 = 34 microM). Compound 5 is a very specific and potent inhibitor of coffee bean alpha-galactosidase (IC50 = 0.71 microM). The glucosides 1 and 7 were potent inhibitors of various alpha-glucosidases, with IC50 values ranging from 1 to 0.1 microM. Furthermore, 1 potently inhibited porcine kidney trehalase (IC50 = 0.013 microM) but failed to inhibit alpha-galactosidase, whereas 7 was a potent inhibitor of alpha-galactosidase (IC50 = 1.7 microM) without trehalase inhibitory activity.
Ikeda
K
K
Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Takahashi
M
M
Nishida
M
M
Miyauchi
M
M
Kizu
H
H
Kameda
Y
Y
Arisawa
M
M
Watson
A A
AA
Nash
R J
RJ
Fleet
G W
GW
Asano
N
N
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D002417:Cattle; D005960:Glucosides / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors; D050112:Imino Pyranoses; D020128:Inhibitory Concentration 50; D007422:Intestines / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010880:Piperidines / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D000470:Alkaloids; D005960:Glucosides; D050112:Imino Pyranoses; D010880:Piperidines; D010936:Plant Extracts; D010940:Plant Proteins; C106502:homonojirimycin; D017485:1-Deoxynojirimycin; D006026:Glycoside Hydrolases