文献类型：期刊文献

英文题名：Design, synthesis and evaluation of novel nitroxide-gentiopicroside hybrids as anti-inflammatory agents with free radical scavenging activity

作者：Wu, Dan[1,2];Cui, Longchen[1];Zhang, Xinyue[1];Xu, Wenkai[1];Peng, Xujing[1,3];Zhang, Qili[1,3];Zhao, Lei[1,3,4,5,6]

第一作者：吴迪;Wu, Dan

通信作者：Zhao, L[1];Zhao, L[2];Zhao, L[3];Zhao, L[4];Zhao, L[5]

机构：[1]Gansu Univ Chinese Med, Coll Pharm, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China;[2]Lanzhou Univ, Hosp 1, 1 Donggang West Rd, Lanzhou 730000, Peoples R China;[3]Gansu Univ Chinese Med, Northwest Collaborat Innovat Ctr Tradit Chinese Me, Lanzhou, Peoples R China;[4]Gansu Univ Chinese Med, Key Lab Chem & Qual TCM Coll Gansu Prov, Lanzhou, Peoples R China;[5]Gansu Univ Chinese Med, Gansu Prov Engn Lab TCM Standardizat Technol & Pop, Lanzhou, Peoples R China;[6]Gansu Pharmaceut Ind Innovat Res Inst, Lanzhou, Peoples R China

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Coll Pharm, 35 Dingxi East Rd, Lanzhou 730000, Peoples R China;[2]corresponding author), Gansu Univ Chinese Med, Northwest Collaborat Innovat Ctr Tradit Chinese Me, Lanzhou, Peoples R China;[3]corresponding author), Gansu Univ Chinese Med, Key Lab Chem & Qual TCM Coll Gansu Prov, Lanzhou, Peoples R China;[4]corresponding author), Gansu Univ Chinese Med, Gansu Prov Engn Lab TCM Standardizat Technol & Pop, Lanzhou, Peoples R China;[5]corresponding author), Gansu Pharmaceut Ind Innovat Res Inst, Lanzhou, Peoples R China.|[10735]甘肃中医药大学;[1073501e14fb35863569f]甘肃中医药大学药学院（西北中藏药协同创新中心办公室）;

年份：2026

外文期刊名：NEW JOURNAL OF CHEMISTRY

收录：;EI(收录号：20262020726833);Scopus(收录号：2-s2.0-105039026283);WOS:【SCI-EXPANDED(收录号:WOS:001766963500001)】；

基金：The authors are grateful for the general financial support of the National Natural Science Foundation of China (nos. 82160457 and 81660577), the Gansu Provincial Department of Education 2024 University Scientific Research Innovation Platform Major Training Project (no. 2024CXPT-18), the Gansu Province Health Industry Scientific Research Project (grant no. GSWSKY2024-45) and the Hospital Fund of the First Hospital of Lanzhou University (grant no. ldyyyn2025-281).

语种：英文

外文关键词：Diseases - Free radicals - Induced polarization logging - Macroinvertebrates - Nitric oxide - Nitrogen oxides - Plants (botany) - Scaffolds (biology)

摘要：Inflammatory processes are often accompanied by oxidative stress, with these two phenomena mutually reinforcing each other in a vicious cycle. Therefore, developing anti-inflammatory agents with ROS scavenging activity is highly meaningful. In this study, 24 novel anti-inflammatory derivatives were designed and synthesized through the hybridization of the COX-2 inhibitor gentiopicroside (GPS) and the ROS scavenging nitroxide radical scaffold. The novel derivatives were subjected to in vitro evaluation of COX-2 inhibitory activity, alongside assessment of free radical scavenging activity using the DPPH assay. The most promising compound GPS-5 exhibited very potent COX-2 inhibitory activity (IC50 = 0.42 & micro;M) and free radical scavenging activity. Furthermore, in RAW 264.7 macrophages, pretreatment with the most promising compound GPS-5 significantly suppressed the LPS-induced production of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and ROS. In addition, GPS-5 was able to attenuate LPS-induced cell polarization. Importantly, in the TPA-induced ear edema model, compound GPS-5 at 0.5 mg per ear achieved 74.5% inhibition, superior to celecoxib (67.8%). Molecular docking studies further showed that GPS-5 exhibits superior binding affinity to the COX-2 (Delta G(bind) = -12.9 kcal mol(-1)) active site compared to celecoxib. These findings establish compound GPS-5 as a promising candidate for the treatment of inflammatory diseases. Furthermore, this work provides a foundation for the development of next-generation anti-inflammatory therapeutics with enhanced potency.