Synthesis and biological evaluation of novel tanshinone IIA derivatives for treating pain.
10.1016/S1875-5364(18)30037-2
- Author:
Qi-Nan LI
1
;
Zhi-Peng HUANG
1
;
Qin-Lan GU
2
;
Zhuo-Er ZHI
1
;
Yu-Han YANG
1
;
Long HE
1
;
Kai-Li CHEN
1
;
Jin-Xin WANG
3
Author Information
1. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 211009, China.
2. Higher Vocational School of Pharmacy, China Pharmaceutical University, Nanjing 211009, China.
3. Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 211009, China. Electronic address: jinxinwang@163.com.
- Publication Type:Journal Article
- Keywords:
Analgesic activity;
MAGL inhibitors;
Tanshinone IIA
- MeSH:
Abietanes;
administration & dosage;
chemical synthesis;
chemistry;
Analgesics;
administration & dosage;
chemical synthesis;
chemistry;
Animals;
Chronic Pain;
drug therapy;
enzymology;
Drug Evaluation, Preclinical;
Enzyme Inhibitors;
administration & dosage;
chemical synthesis;
chemistry;
Female;
Humans;
Male;
Mice;
Mice, Inbred ICR;
Monoacylglycerol Lipases;
antagonists & inhibitors;
metabolism;
Structure-Activity Relationship
- From:
Chinese Journal of Natural Medicines (English Ed.)
2018;16(2):113-124
- CountryChina
- Language:English
-
Abstract:
Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.
