Absolute stereostructure of potent alpha-glucosidase inhibitor, Salacinol, with unique thiosugar sulfonium sulfate inner salt structure from Salacia reticulata.
A most potent alpha-glucosidase inhibitor named salacinol has been isolated from an antidiabetic Ayurvedic traditional medicine, Salacia reticulata WIGHT, through bioassay-guided separation. The absolute stereostructure of salacinol was determined on the basis of chemical and physicochemical evidence, which included the alkaline degradation of salacinol to 1-deoxy-4-thio-D-arabinofuranose and the X-ray crystallographic analysis, to be the unique spiro-like configuration of the inner salt comprised of 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation and 1'-deoxy-D-erythrosyl-3'-sulfate anion. Salacinol showed potent inhibitory activities on several alpha-glucosidases, such as maltase, sucrase, and isomaltase, and the inhibitory effects on serum glucose levels in maltose- and sucrose-loaded rats (in vivo) were found to be more potent than that of acarbose, a commercial alpha-glucosidase inhibitor.
Yoshikawa
Masayuki
M
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, 607-8412, Kyoto, Japan. shoyaku@mb.kyoto-phu.ac.jp
Morikawa
Toshio
T
Matsuda
Hisashi
H
Tanabe
Genzoh
G
Muraoka
Osamu
O
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D029753:Celastraceae / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D008297:Male; D008515:Medicine, Ayurvedic; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000737:chemistry / Q000302:isolation & purification* / Q000493:pharmacokinetics*; D013431:Sulfates; D000520:alpha-Glucosidases / Q000378:metabolism
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D013402:Sugar Alcohols; D013431:Sulfates; C427963:salacinol; D000520:alpha-Glucosidases