Synthesis, and anti-inflammatory activities of gentiopicroside derivatives.
10.1016/S1875-5364(22)60187-0
- Author:
Qi-Li ZHANG
1
;
Peng-Fei XIA
2
,
3
,
4
;
Xue-Jing PENG
2
,
3
,
4
;
Xiao-Yu WU
2
,
3
,
4
;
Hua JIN
1
;
Jian ZHANG
2
,
3
,
5
;
Lei ZHAO
2
,
3
,
6
Author Information
1. Gansu University of Chinese Medicine, Lanzhou 730000, China.
2. Gansu University of Chinese Medicine, Lanzhou 730000, China
3. Key Laboratory of Chemistry and Quality of TCM of the College of Gansu Province, Lanzhou 730000, China
4. Gansu Province Engineering Laboratory for TCM Standardization Technology and Popularization, Lanzhou 730000, China.
5. Gansu Province Engineering Laboratory for TCM Standardization Technology and Popularization, Lanzhou 730000, China. Electronic address: zhangjian08@lzu.edu.cn.
6. Gansu Province Engineering Laboratory for TCM Standardization Technology and Popularization, Lanzhou 730000, China. Electronic address: zzyhx@gszy.edu.cn.
- Publication Type:Journal Article
- Keywords:
Anti-inflammatory activity;
Gentiopicroside derivatives;
Selective inhibitors;
Structural modification
- MeSH:
Animals;
Anti-Inflammatory Agents/pharmacology*;
Cyclooxygenase 2/chemistry*;
Dinoprostone;
Interleukin-6/metabolism*;
Iridoid Glucosides;
Mice;
Molecular Docking Simulation;
Pyridinolcarbamate
- From:
Chinese Journal of Natural Medicines (English Ed.)
2022;20(4):309-320
- CountryChina
- Language:English
-
Abstract:
A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.
