title: Antagonistic effects of extracts from Artemisia rupetris L. and Leontopodium leontopodioides to CC chemokine receptor 2b (CCR2b).
abstract: The present study was designed to establish a suitable assay to explore CCR2b receptor antagonists from the natural products of Artemisia rupetris and Leontopodium leontopodioides. An aequorin assay was developed as a cell-based assay suitable for 384-well microplate and used for screening CCR2b receptor antagonists from natural products. Through establishing suitable conditions, the assay was shown to be suitable for screening of CCR2b receptor antagonists. Seven compounds were identified in preliminary screening. Five of them showed evident dose-response relationship in secondary screening. The structure-activity relationship study suggested that 7-position hydroxyl group of flavonoids was necessary, a polar group should be introduced on the 3-position, and the substituents on 2-position benzene ring of flavonoids have little influence on the potentency of the inhibition activity on CCR2b receptor. The ortho-position dihydroxyl structure in quinic acid compounds may be important. In conclusion, Compounds HR-1, 5, 7, and AR-20, 35 showed activity as antagonist of CCR2b receptor, which shed lights on the development of novel drugs as CCR2b receptor antagonists for preventing inflammation related diseases.
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qin-Wei
authors.initials: QW
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qiu-Bin
authors.initials: QB
authors.lastname: Yang
authors.affiliation: School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Sun
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance (China Pharmaceutical University), Ministry of Education, Nanjing 210009, China. Electronic address: lyzhang@cpu.edu.cn.
authors.forename: Lu-Yong
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China. Electronic address: brookming@cpu.edu.cn.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
mesh_terms: D019306:Artemisia / Q000737:chemistry*; D019659:Asteraceae / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007700:Kinetics; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D010936:Plant Extracts; D054390:Receptors, CCR2
keywords: Aequorin assay; Artemisia rupetris; CCR2b antagonist; Inflammation; Leontopodium leontopodioides