文献类型：期刊文献

英文题名：Coptisine, a natural alkaloid from Coptidis Rhizoma, inhibits plasmodium falciparum dihydroorotate dehydrogenase

作者：Lang, Li[1];Hu, Qian[1];Wang, Jingyuan[1];Liu, Zehui[1];Huang, Jin[1];Lu, Weiqiang[2,3];Huang, Ying[4]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai, Peoples R China;[3]East China Univ Sci & Technol, Sch Life Sci, Shanghai, Peoples R China;[4]Guangdong Inst Drug Control, Guangzhou, Guangdong, Peoples R China

年份：2018

卷号：92

期号：1

起止页码：1324

外文期刊名：CHEMICAL BIOLOGY & DRUG DESIGN

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000436403500015)】；

基金：The work is supported by the National Natural Science Foundation of China (81773775); Shanghai Committee of Science and Technology (15431902000); State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University; CMEMR2017-B01).

语种：英文

外文关键词：coptisine; dihydroorotate dehydrogenase; plasmodium falciparum; pyrimidine biosynthesis; traditional Chinese medicine

摘要：Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is a promising drug target for antimalarial chemotherapy. In our continuous efforts to develop more potent PfDHODH inhibitors, a unique library of active ingredients from traditional Chinese medicine (TCM) has been collected and was screened in this study. Through the initial screening, we found that coptisine, a natural alkaloid from TCM Coptidis Rhizoma, was a novel and potent inhibitor of PfDHODH with an IC50 value of 1.83 +/- 0.08m. At the same time, enzyme kinetic analysis using Lineweaver-Burk plot indicated that coptisine is an uncompetitive inhibitor for PfDHODH. Thermal shift assay and molecular docking simulation research reveal that coptisine is capable of binding with PfDHODH. Moreover, coptisine exhibits weak inhibition activity against human DHODH, indicating that coptisine is a selective inhibitor of PfDHODH. Taken together, our study highlights the potential of active ingredients in TCM as valuable resource for discovering novel chemical scaffolds for PfDHODH.