Hydroxycoumarin derivatives: novel and potent α-glucosidase inhibitors.
A novel class of hydroxycoumarin derivatives were found to be potent α-glucosidase inhibitors. Their syntheses were reported and the structure-activity relationship was established. Kinetic enzymatic assays indicated that compound 10 was a slow-binding and noncompetitive inhibitor with a Ki value of 589 nM, while compound 11 was a competitive inhibitor with a Ki value of 4.810 μM. Among all hydroxycoumarin derivatives studied, compounds 10 and 11 exhibited the highest activities, were specific inhibitors of α-glucosidase, and could be exploited as the lead compounds for the development of potent α-glucosidase inhibitors. Compounds 10 and 11 were also selected for further discussion for the mechanism of enzymatic inhibition.
School of Pharmacy and Centre for Biomolecular Science, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.
Qiong
Q
Shen
Jialiang
J
Shao
Quan
Q
Peng
Wanjin
W
Zhang
Lin
L
Ma
Albert S C
AS
Chan
Lianquan
L
Gu
D002942:Circular Dichroism; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D006860:Hydrogen Bonding; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism
D003374:Coumarins; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D000520:alpha-Glucosidases