虎耳草素类似物作为β-分泌酶（BACE1）抑制剂的构效关系。
Structure-activity relationships for bergenin analogues as β-secretase (BACE1) inhibitors.
作者信息
Kashima Yusei, Miyazawa Mitsuo
机构信息
Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University, Osaka, Japan.
出版信息
J Oleo Sci. 2013;62(6):391-401. doi: 10.5650/jos.62.391.
Here we evaluated the inhibitory effects of bergenin analogues (2-10), prepared from naturally occurring bergenin, (1) on β-secretase (BACE1) activity. All the bergenin analogues that were analyzed inhibited BACE1 in a dose-dependent manner. 11-O-protocatechuoylbergenin (5) was the most potent inhibitor, with an IC₅₀ value of 0.6 ± 0.07 μM. The other bergenin analogues, in particular, 11-O-3',4'-dimethoxybenzoyl)-bergenin (6), 11-O-vanilloylbergenin (7), and 11-O-isovanilloylbergenin (8), inhibited BACE1 activity with IC₅₀ values of <10.0 μM. BACE1 inhibitory activity was influenced by the substituents of the benzoic acid moiety. To the best of our knowledge, this is the first report on the structure-activity relationships (SAR) in the BACE1 inhibitory activities of bergenin analogues. These bergenin analogues may be useful in studying the mechanisms of Alzheimer's disease.
在此，我们评估了由天然存在的岩白菜素（1）制备的岩白菜素类似物（2 - 10）对β-分泌酶（BACE1）活性的抑制作用。所有分析的岩白菜素类似物均以剂量依赖性方式抑制BACE1。11 - O - 原儿茶酰岩白菜素（5）是最有效的抑制剂，IC₅₀值为0.6±0.07μM。其他岩白菜素类似物，特别是11 - O - （3'，4'-二甲氧基苯甲酰基）-岩白菜素（6）、11 - O - 香草酰岩白菜素（7）和11 - O - 异香草酰岩白菜素（8），抑制BACE1活性的IC₅₀值<10.0μM。BACE1抑制活性受苯甲酸部分取代基的影响。据我们所知，这是关于岩白菜素类似物对BACE1抑制活性的构效关系（SAR）的首次报道。这些岩白菜素类似物可能有助于研究阿尔茨海默病的发病机制。
Zotero 插件