Synthesis and monoamine oxidase B inhibitory activities of isoquiritigenin derivatives.
10.19540/j.cnki.cjcmm.20190807.201
- Author:
Zhuo KONG
1
;
De-Meng SUN
1
;
Ai-Qian CHEN
1
;
Yun HU
1
Author Information
1. Department of Bioengineering,Zhuhai Campus,Zunyi Medical University Zhuhai 519041,China.
- Publication Type:Journal Article
- Keywords:
MAO-B inhibitor;
competitive inhibitor;
isoliquiritigenin;
structure-activity relationship
- MeSH:
Animals;
Drugs, Chinese Herbal;
Humans;
Monoamine Oxidase;
Monoamine Oxidase Inhibitors;
Plant Extracts;
Rats;
Structure-Activity Relationship
- From:
China Journal of Chinese Materia Medica
2019;44(21):4653-4660
- CountryChina
- Language:Chinese
-
Abstract:
Isoquiritigenin,one of the active constituents in the Chinese herb liquorice,is found to have moderate inhibitory activity against rat monoamine oxidase B(MAO-B,IC5047. 2 μmol·L-1). However,the structure-activity relationship(SAR) remains unclear until now. In an attempt to reveal the SAR of inhibition by isoquiritigenin,and to identify more potent and selective inhibitors of MAOB,a series of 13 derivatives based on the scaffold of isoquiritigenin were prepared,and their purities and structures were confirmed by UPLC,1 H-NMR,13 C-NMR and HRMS. These compounds were then evaluated for their ability to inhibit the enzymatic activity of human MAO-B. The SAR of inhibition was summarized and a potent compound C8 with high inhibitory activity(IC501. 4 μmol·L-1) and selectivity(>57 folds over MAO-A) was identified. Enzyme kinetics studies suggested that C8 acted as a competitive inhibitor. In addition,C8 showed little cytotoxicity to glial cells in vitro,which could be a promising lead compound for further study.
