A novel competitive class of α-glucosidase inhibitors: (E)-1-phenyl-3-(4-styrylphenyl)urea derivatives.
Competitive glycosidase inhibitors are generally sugar mimics that are costly and tedious to obtain because they require challenging and elongated chemical synthesis, which must be stereo- and regiocontrolled. Here, we show that readily accessible achiral (E)-1-phenyl-3-(4-strylphenyl)ureas are potent competitive α-glucosidase inhibitors. A systematic synthesis study shows that the 1-phenyl moiety on the urea is critical for ensuring competitive inhibition, and substituents on both terminal phenyl groups contribute to inhibition potency. The most potent inhibitor, compound 12 (IC(50)=8.4 μM, K(i)=3.2 μM), manifested a simple slow-binding inhibition profile for α-glucosidase with the kinetic parameters k(3)=0.005256 μM(-1) min(-1), k(4)=0.003024 min(-1), and K(i)(app) =0.5753 μM.
Kim
Jun Young
JY
Division of Applied Life Science, Gyeongsang National University, Jinju, South Korea.
Lee
Ji Won
JW
Kim
Young Soo
YS
Lee
Yuno
Y
Ryu
Young Bae
YB
Kim
Songmi
S
Ryu
Hyung Won
HW
Curtis-Long
Marcus J
MJ
Lee
Keun Woo
KW
Lee
Woo Song
WS
Park
Ki Hun
KH
D001667:Binding, Competitive; D004791:Enzyme Inhibitors / Q000737:chemistry*; D065089:Glycoside Hydrolase Inhibitors; D007700:Kinetics; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry; D000520:alpha-Glucosidases / Q000378:metabolism
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D010671:Phenylurea Compounds; D014508:Urea; D000520:alpha-Glucosidases