A beta-secretase (BACE1) inhibitor hispidin from the mycelial cultures of Phellinus linteus.
In the course of screening for anti-dementia agents from natural products, a beta-secretase (BACE1) inhibitor was isolated from the culture broth of Phellinus linteus and identified as hispidin. It showed an IC (50) value of 4.9 x 10 (-6) M and a Ki value of 8.4 x 10 (-6) M. The compound was a non-competitive inhibitor. Hispidin also inhibited a prolyl endopeptidase (IC (50) = 1.6 x 10 (-5) M, Ki = 2.4 x 10 (-5) M), but it was less inhibitory to alpha-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase.
Park
In-Hye
IH
Division of Applied Biology and Chemistry, College of Agriculture and Life Sciences, Kyungpook National University, Daegu, Korea.
Jeon
So-Young
SY
Lee
Hee-Ju
HJ
Kim
Sang-In
SI
Song
Kyung-Sik
KS
D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D010450:Endopeptidases; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005658:Fungi; D006801:Humans; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011753:Pyrones / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D010936:Plant Extracts; D011753:Pyrones; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C007946:hispidin