Synthesis, and anti-inflammatory activities of gentiopicroside derivatives.
10.1016/S1875-5364(22)60187-0
- Author:
Qi-Li ZHANG
1
;
Peng-Fei XIA
2
;
Xue-Jing PENG
2
;
Xiao-Yu WU
2
;
Hua JIN
1
;
Jian ZHANG
3
;
Lei ZHAO
4
Author Information
1. Gansu University of Chinese Medicine, Lanzhou 730000, China.
2. Gansu University of Chinese Medicine, Lanzhou 730000, China; Key Laboratory of Chemistry and Quality of TCM of the College of Gansu Province, Lanzhou 730000, China; Gansu Province Engineering Laboratory for TCM Standardization Technology and Popularization, Lanzhou 730000, China.
3. Gansu University of Chinese Medicine, Lanzhou 730000, China; Key Laboratory of Chemistry and Quality of TCM of the College of Gansu Province, Lanzhou 730000, China; Gansu Province Engineering Laboratory for TCM Standardization Technology and Popularization, Lanzhou 730000, China. Electronic address: zhangjian08@lzu.edu.cn.
4. Gansu University of Chinese Medicine, Lanzhou 730000, China; Key Laboratory of Chemistry and Quality of TCM of the College of Gansu Province, Lanzhou 730000, China; 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.
