Structure-activity relationships for alpha-glucosidase inhibition of baicalein, 5,6,7-trihydroxyflavone: the effect of A-ring substitution.
In order to estimate the effects of the A-ring hydroxyl group of baicalein (5,6,7-trihydroxyflavone, 1) on rat intestinal alpha-glucosidase inhibition, flavone, monohydroxyflavones, dihydroxyflavones, and methylated derivatives of 5,6,7-trihydroxyflavone were used for the structure-activity relationship (SAR) study. The importance of the 6-hydroxyl group of baicalein was validated for an exertion of the activity. And also, the tested flavones which lacked a hydroxyl substituent on any of positions 5, 6, or 7, showed no activity. Hence, the 5,6,7-trihydroxyflavone structure was concluded to be crucial for the potent inhibitory activity. In addition, an introduction of electron-withdrawing or electron-donating groups at position 8 of baicalein led to a dramatic decrease for activity, except for 8-fluoro-5,6,7-trihydroxyflavone, which carried a less bulky substituent on position 8. Hence, this result suggested that a sterically bulky substituent on C-8 of baicalein was detrimental for the activity regardless of its electronic nature. Through examining the inhibitory mechanism of baicalein against rat intestinal alpha-glucosidase, it was suggested to be a mixed type inhibition.
Laboratory of Food Biochemistry, Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.
Hong
H
Gao
Tetsuo
T
Nishioka
Jun
J
Kawabata
Takanori
T
Kasai
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D044950:Flavanones; D005419:Flavonoids / Q000138:chemical synthesis / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D006900:Hydroxylation; D007202:Indicators and Reagents; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D065089:Glycoside Hydrolase Inhibitors; D007202:Indicators and Reagents; C006680:baicalein