beta-Secretase (BACE-1) inhibitory effect of biflavonoids

Hiroaki Sasaki; Kazuhiko Miki; Kaoru Kinoshita; Kiyotaka Koyama; Lia D Juliawaty; Sjamsul A Achmad; Euis H Hakim; Miyuki Kaneda; Kunio Takahashi

doi:10.1016/j.bmcl.2010.06.021

beta-Secretase (BACE-1) inhibitory effect of biflavonoids

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4558-60. doi: 10.1016/j.bmcl.2010.06.021. Epub 2010 Jun 8.

Authors

Hiroaki Sasaki¹, Kazuhiko Miki, Kaoru Kinoshita, Kiyotaka Koyama, Lia D Juliawaty, Sjamsul A Achmad, Euis H Hakim, Miyuki Kaneda, Kunio Takahashi

Affiliation

¹ School of Pharmacy, Shujitsu University, Naka-ku, Okayama 703-8516, Japan.

PMID: 20598535
DOI: 10.1016/j.bmcl.2010.06.021

Abstract

Here, we describe amentoflavone-type biflavonoids, which were isolated from natural sources and were found to inhibit beta-secretase (BACE-1). The structure-activity relationship was studied, and compounds 1-8, 10, 17, and 18 showed BACE-1 inhibitory activity. Among these compounds, 2,3-dihydroamentoflavone 17 and 2,3-dihydro-6-methylginkgetin 18 exhibited potent inhibitory effects with IC(50) values of 0.75 and 0.35 microM, respectively.

MeSH terms

Amyloid Precursor Protein Secretases / antagonists & inhibitors*
Amyloid Precursor Protein Secretases / metabolism
Biflavonoids / chemistry*
Biflavonoids / pharmacology
Protease Inhibitors / chemistry*
Protease Inhibitors / pharmacology
Structure-Activity Relationship

Substances

2,3-dihydro-6-methylginkgetin
2,3-dihydroamentoflavone
Biflavonoids
Protease Inhibitors
Amyloid Precursor Protein Secretases