alpha-Glucosidase inhibition of 6-hydroxyflavones. Part 3: Synthesis and evaluation of 2,3,4-trihydroxybenzoyl-containing flavonoid analogs and 6-aminoflavones as alpha-glucosidase inhibitors.
The SAR studies suggested that the C-ring of baicalein (1) was not necessary for the activity, and validated the importance of 2,3,4-trihydroxybenzoyl structure of 1. Thus, a series of 2,3,4-trihydroxybenzoyl-containing flavonoid analogs were investigated for the alpha-glucosidase inhibitory activity. The results indicated that 5,6,7-trihydroxy-2-phenyl-4-quinolone (2) and 5,6,7-trihydroxyflavanone (4) showed the comparable activity to 1, while 3,5,6,7-tetrahydroxyflavone (7), 5,6,7-trihydroxyisoflavone (8), and 6-hydroxygenistein (9) showed moderate alpha-glucosidase inhibitory activity. In addition, it was found that 6-amino-5,7-dihydroxyflavone (16) was a more potent and specific rat intestinal alpha-glucosidase inhibitor than 1, and showed the comparable activity to acarbose. This is the first report on mammalian intestinal alpha-glucosidase inhibitory activity of 6-aminoflavones. Kinetic studies revealed that 16 inhibited both sucrose- and maltose-hydrolyzing activities of rat intestinal alpha-glucosidase uncompetitively.
Gao
Hong
H
Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo 060-8589, Japan.
Kawabata
Jun
J
D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013552:Swine
D004791:Enzyme Inhibitors; D047309:Flavones; D065089:Glycoside Hydrolase Inhibitors