文献类型：期刊文献

英文题名：In Vitro Human Dihydroorotate Dehydrogenase Inhibitory, Anti-inflammatory and Cytotoxic Activities of Alkaloids from the Seeds of Nigella glandulifera

作者：Gao, Jun-Bo[1,6];Zhang, Xing-Jie[2,3];Zhang, Rui-Han[2,3];Zhu, Li-Li[5];Pu, De-Bing[2,3];Li, Xiao-Li[2,3];Li, Hong-Lin[5];Xu, Min[4];Xiao, Wei-Lie[1,2,3]

机构：[1]Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming, Yunnan, Peoples R China;[2]Yunnan Univ, Key Lab Med Chem Nat Resource, Minist Educ, Sch Chem Sci & Technol, 2 North Cuihu Rd, Kunming 650091, Yunnan, Peoples R China;[3]Yunnan Univ, State Key Lab Conservat & Utilizat Bioresources Y, Kunming, Yunnan, Peoples R China;[4]Southeast Univ, Sch Med, Dept Pharmacol, 87 Dingjiaqiao Rd, Nanjing 210096, Jiangsu, Peoples R China;[5]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai, Peoples R China;[6]Univ Chinese Acad Sci, Beijing, Peoples R China

年份：2018

卷号：84

期号：14

起止页码：1013

外文期刊名：PLANTA MEDICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000444454300003)】；

基金：This research was supported financially by grants from the Natural Science Foundation of China (81422046 and 21762048) and the Program for Changjiang Scholars and Innovative Research Team in University (IRT_17R94).

语种：英文

外文关键词：dolabellane-type diterpene alkaloids; Ranunculaceae; Nigella glandulifera; human dihydroorotate dehydrogenase; lipopolysaccharide; nitric oxide production; cytotoxic activity

摘要：Four new dolabellane-type diterpene alkaloids, glandulamines A-D (1-4), together with twelve known compounds (5-16), were isolated from the seeds of Nigella glandulifera using repeated column chromatography and semipreparative HPLC. The structures of 1-16 were elucidated based on NMR data analysis, HRMS experiments and other spectroscopic interpretations. The absolute configuration of 5 was determined by single-crystal X-ray diffraction data for the first time. Compounds 10 and 12 showed human dihydroorotate dehydrogenase inhibitory activity with IC50 values of 61.1 +/- 5.3 and 45.9 +/- 3.0 mu M, respectively. Molecular docking of the active compound 12 and positive control teriflunomide on the inhibitor-binding site of human dihydroorotate dehydrogenase was subsequently performed to visualize the interaction pattern. In addition, compounds 8 and 10 exhibited inhibitory effects against lipopolysaccharide-induced nitric oxide production with inhibition rates of 61 and 41%, respectively, at the concentration of 10 mu M. Compounds 9 and 12 showed cytotoxic activities with cell viability varying from 29 +/- 57% at 100 mu M against T98G, U87, U251, and GL261 glioma cancer cell lines. These data provide new insights on the pharmacologically active compounds of this plant widely used in folk medicine.