Structure-activity relationships for naturally occurring coumarins as ¦Â-secretase inhibitor

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• 作者：Shinsuke Marumoto ; Mitsuo Miyazawa ; ^{miyazawa@apch.kindai.ac.jp}
• 关键词：Coumarin ; Furanocoumarin ; Pyranocoumarin ; ¦Â-Secretase ; Structure&ndash ; activity relationships
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 出版时间：15 January, 2012
• 年：2012
• 卷：20
• 期：2
• 页码：784-788
• 全文大小：273 K

文摘

The present study was demonstrated to evaluate the effects of naturally occurring coumarins (NOCs) including simple coumarins, furanocoumarins, and pyranocoumarins on the inhibition of ¦Â-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 IC₅₀ value of 9.9 ¦ÌM. Other furanocoumarin derivatives, for example, 8-geranyloxy-5-methoxypsoralen (35), 8-geranyloxypsoralen (24), and bergamottin (18) inhibited BACE1 activity, with the IC₅₀ values <25.0 ¦ÌM. 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.