Synthesis,and anti-inflammatory activities of gentiopicroside derivatives  

作　　者：ZHANG Qi-Li XIA Peng-Fei PENG Xue-Jing WU Xiao-Yu JIN Hua ZHANG Jian ZHAO Lei 

机构地区：[1]Gansu University of Chinese Medicine,Lanzhou 730000,China [2]Key Laboratory of Chemistry and Quality of TCM of the College of Gansu Province,Lanzhou 730000,China [3]Gansu Province Engineering Laboratory for TCM Standardization Technology and Popularization,Lanzhou 730000,China

出　　处：《Chinese Journal of Natural Medicines》2022年第4期309-320,共12页中国天然药物（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.82160457 and 81660577);the Natural Science Foundation of Gansu Province(No.21JR7RA564).

摘　　要：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.

关 键 词：Gentiopicroside derivatives Structural modification Anti-inflammatory activity Selective inhibitors 

分 类 号：R284[医药卫生—中药学] R965[医药卫生—中医学]