β-Secretase (BACE1) Inhibitors from Perilla frutescens var. acuta
β-Secretase (BACE1) Inhibitors from Perilla frutescens var. acuta
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DOI：
10.1007/s12272-001-1139-9
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发表时间：
2008-02-01
影响因子：
6.7
通讯作者：
Song, Kyung-Sik
中科院分区：
文献类型：
--
作者：
Choi, Sun-Ha;Hur, Jong-Moon;Song, Kyung-Sik
在从天然产物中筛选抗痴呆药物的过程中，从紫苏醇提物中分离到两个β-分泌酶(BACE1)抑制剂。鉴定为木犀草素(1)和迷迭香酸(2)，其IC50值分别为5.0×10(-7)M和2.1×10(-5)M。在Dixon图谱中，它们以非竞争性方式抑制BACE1与底物，这表明它们可能与P-分泌酶亚基或另一个调控位点结合。KI值分别为6.2×10~(-5)M和3.9×10~(-5)M。它们对其他酶如α-分泌酶(TACE)、乙酰胆碱酯酶(AChE)、胰凝乳酶和弹性蛋白酶的抑制作用较弱，表明它们是BACE1的相对特异的抑制剂。
In the course of screening for anti-dementia agents from natural products, two P-secretase (BACE1) inhibitors were isolated from the methanolic extract of Perilla frutescens var. acuta and identified as luteolin (1) and rosmarinic acid (2) with IC50 values of 5.0 x 10(-7) M and 2.1 x 10(-5) M, respectively. They inhibited BACE1 in a non-competitive manner with a substrate in Dixon plots, suggesting that they might bind to either P-secretase subsite or to another regulatory site. Ki values of 1 and 2 were 6.2 x 10(-5) M and 3.9 x 10(-5) M, respectively. They were less inhibitory against other enzymes such as a-secretase (TACE), acetylcholine esterase (AchE), chymotrypsin, and elastase, indicating that they were relatively specific inhibitors of BACE1.