Importance of the B ring and its substitution on the alpha-glucosidase inhibitory activity of baicalein, 5,6,7-trihydroxyflavone.
Hydroxychromones and B-ring-substituted 5,6,7-trihydroxyflavones were prepared to evaluate the contribution of the B ring of baicalein (5,6,7-trihydroxyflavone, 1) to its potent alpha-glucosidase inhibitory activity. Hydroxychromones, which lack 6-hydroxyl substitution, did not show any inhibitory activity, while 5,6,7-trihydroxy-2-methylchromone (5) showed high activity. Among the tested B-ring-substituted 5,6,7-trihydroxyflavones, the 4'-hydroxy-, 3',4'-dihydroxy-, and 3',4',5'-trihydroxy-substituted derivatives were found to give more activity than that of 1. The methoxy-substituted derivatives, however, showed less activity than 1. The results suggest that the B ring of 1 was not essential, although advantageous to the activity; hydroxyl substitution on the B ring of 5,6,7-trihydroxyflavones was favorable to the activity, whereas methoxyl substitution was unfavorable; at least 4'-hydroxyl substitution of 5,6,7-trihydroxyflavones was required for enhanced activity, in which the number of hydroxyl groups did not take part.
Gao
Hong
H
Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan.
Kawabata
Jun
J
D000818:Animals; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D044950:Flavanones / Q000737:chemistry* / Q000494:pharmacology*; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D020128:Inhibitory Concentration 50; D007422:Intestines / Q000201:enzymology; D051381:Rats; D013329:Structure-Activity Relationship
D002867:Chromones; D004791:Enzyme Inhibitors; D044950:Flavanones; D047309:Flavones; D065089:Glycoside Hydrolase Inhibitors; C006680:baicalein