Green tea catechins as a BACE1 (beta-secretase) inhibitor.
In the course of searching for BACE1 (beta-secretase) inhibitors from natural products, the ethyl acetate soluble fraction of green tea, which was suspected to be rich in catechin content, showed potent inhibitory activity. (-)-Epigallocatechin gallate, (-)-epicatechin gallate, and (-)-gallocatechin gallate were isolated with IC(50) values of 1.6 x 10(-6), 4.5 x 10(-6), and 1.8 x 10(-6) M, respectively. Seven additional authentic catechins were tested for a fundamental structure-activity relationship. (-)-Catechin gallate, (-)-gallocatechin, and (-)-epigallocatechin significantly inhibited BACE1 activity with IC(50) values of 6.0 x 10(-6), 2.5 x 10(-6), and 2.4 x 10(-6) M, respectively. However, (+)-catechin, (-)-catechin, (+)-epicatechin, and (-)-epicatechin exhibited about ten times less inhibitory activity. The stronger activity seemed to be related to the pyrogallol moiety on C-2 and/or C-3 of catechin skeleton, while the stereochemistry of C-2 and C-3 did not have an effect on the inhibitory activity. The active catechins inhibited BACE1 activity in a non-competitive manner with a substrate in Dixon plots.
Division of Applied Biology & Chemistry, College of Agriculture & Life Sciences, Kyungpook National University, 1370 Sankyuk-Dong, Daegu 702-701, South Korea.
So-Young
SY
Jeon
KiHwan
K
Bae
Yeon-Hee
YH
Seong
Kyung-Sik
KS
Song
D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002392:Catechin / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010450:Endopeptidases; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D013662:Tea
D011480:Protease Inhibitors; D013662:Tea; D002392:Catechin; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases