2. Academic Validation
  3. Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor

Structure-activity relationships for naturally occurring coumarins as β-secretase inhibitor

  • Bioorg Med Chem. 2012 Jan 15;20(2):784-8. doi: 10.1016/j.bmc.2011.12.002.
Shinsuke Marumoto 1,  Mitsuo Miyazawa
Affiliations

Affiliation

  • 1 Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Kowakae, Higashiosaka-shi, Osaka 577-8502, Japan.
PMID: 22222157 DOI: 10.1016/j.bmc.2011.12.002
Abstract

The present study was demonstrated to evaluate the effects of naturally occurring Coumarins (NOCs) including simple Coumarins, furanocoumarins, and pyranocoumarins on the inhibition of β-secretase (BACE1) activity. Of 41 NOCs examined, some furanocoumarins inhibited BACE1 activity, but simple Coumarins and pyranocoumarins did not affect. The most potent inhibitor was 5-geranyloxy-8-methoxypsoralen (31), which has an IC(50) value of 9.9 μM. Other furanocoumarin derivatives, for example, 8-geranyloxy-5-methoxypsoralen (35), 8-geranyloxypsoralen (24), and bergamottin (18) inhibited BACE1 activity, with the IC(50) values <25.0 μM. Analyses of the inhibition mechanism by Dixon plots and Cornish-Bowden plots showed that compounds 18, 31 and 35 were mixed-type inhibitor. The kinetics of inhibition of BACE1 by Coumarins 24 was non-competitive inhibitors.

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