Screening succinate semialdehyde dehydrogenase inhibitors:an estab-lished model and its application in Tall Gastrodia Tuber
10.3969/j.issn.1006-2157.2016.08.011
- VernacularTitle:琥珀酸半醛脱氢酶抑制剂筛选方法的建立及其在天麻成分筛选中的应用
- Author:
Bi LI
1
;
Xiong FANG
;
Fuhao CHU
;
Bing XU
;
Siling BI
;
Chenze ZHANG
;
Wenqiang YAN
;
Yuzhong ZHANG
;
Penglong WANG
;
Haimin LEI
Author Information
1. 北京中医药大学中药学院 北京 100102
- Keywords:
inhibitor of succinate semialdehyde dehydrogenase;
structure-activity relationship;
anti-epi-lepsy;
Rhizoma Gastrodiae;
4-hydroxybenzaldehyde;
high throughput screening
- From:
Journal of Beijing University of Traditional Chinese Medicine
2016;39(8):664-669
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a model of screening succinate semialdehyde dehydrogenase (SSADH)inhibitors with anti-epilepsy effects,then using this model to find out the effective components in Tall Gastrodia Tuber (Latin:Rhizoma Gastrodiae,pinyin:Tianma)and some analogues and to study their structure-activity relationship.Methods First,SSADH enzyme system fluid was prepared,and the correlation of activity and optical density of SSADH was evaluated using UV spectrophotometry.Then,af-ter the screening method of SSADH activity was established by optimization of reaction temperature,reac-tion time,concentration of NAD +,SSA and SSADH,and pH of buffer on the SSADH activity,p-hydroxybenzaldehyde (HBA),a positive drug recorded in literature,was applied to verify the model. And the structural analogues of HBA were measured and the mechanism was analyzed.Results The screening model was established successfully,proved by HBA test.The UV detective system and its buff-ers of SSADH activity were determined with reaction temperature at 37 ℃ for 30 min,and detect wave at 340 nm.The structure-activity of HBA on GABA-T was as the same as that of vanillic aldehyde,and—OH and —CHO of benzene ring were the essential groups for inhibition SSADH.Conclusion The model established in this paper can be used for high throughput screening SSADH inhibitors and may guide the study of analogues of SSADH inhibitors and their mechanism.
