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Synthetic Analogues of Betulinic Acid as Potent Inhibitors of PS1 / BACE1 Interaction to Reduce Aβ Generation
Author(s) -
Zhang Chenlu,
Wang Xiaoyin,
Cui Jin,
Li Xiaohang,
Zhang Yangming,
Wang Xin,
Gu Haifeng,
Li Wei,
Xie Xin,
Zhao Jian,
Pei Gang,
Nan Fajun
Publication year - 2017
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.201600611
Subject(s) - chemistry , betulinic acid , lead compound , terpene , triterpenoid , amyloid precursor protein , stereochemistry , combinatorial chemistry , biochemistry , pharmacology , computational biology , in vitro , alzheimer's disease , disease , medicine , genetics , biology , pathology
The lupane‐type triterpenoids are endowed with a wide range of biological activities such as antiviral, anti‐inflammatory and anticancer activity. We describe here its potential application in Alzheimer's disease ( AD ) treatment as an inhibitor of PS1 / BACE1 interaction. 3‐ α ‐Akebonoic acid, which emanated from a high throughput screening ( HTS ), was discovered to interfere with PS1 / BACE1 interaction and reduce amyloid β‐protein (Aβ) production. In view of the limited source, we instead used naturally rich betulinic acid (compound 2 ) as starting material for lead optimization and a focused library of its derivatives was constructed to gain a better understanding of the structure activity relationship ( SAR ) of triterpenoid‐type inhibitor of PS1 / BACE1 interaction. Compound 22 was finally chosen as the most potent PS1 / BACE1 interaction inhibitor, which reduced Aβ generation effectively.