title: Synthesis and biological evaluation of methylated scutellarein analogs based on metabolic mechanism of scutellarin in vivo.
abstract: Scutellarin (1) could be hydrolyzed into scutellarein (2) in vivo and then converted into methylated, sulfated and glucuronidated forms. In order to investigate the biological activities of these methylated metabolites, eight methylated analogs of scutellarein (2) were synthesized via semi-synthetic methods. The antithrombotic activities of these compounds were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). Their antioxidant activities were assessed by measuring their scavenging capacities toward 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and the ability to protect PC12 cells against H2O2-induced cytotoxicity. Furthermore, the physicochemical properties of these compounds including aqueous solubility and lipophilicity were also investigated. The results showed that 6-O-methylscutellarein (5) demonstrated potent antithrombotic activity, stronger antioxidant activity and balanced solubility and permeability compared with scutellarin (1), which warrants further development of 5 as a promising lead for the treatment of ischemic cerebrovascular disease.
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China; Department of Organic Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 211198, PR China.
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Shi
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China. Electronic address: linianguang@njutcm.edu.cn.
authors.forename: Nian-Guang
authors.initials: NG
authors.lastname: Li
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.
authors.forename: Zhen-Jiang
authors.initials: ZJ
authors.lastname: Wang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China. Electronic address: yupingtang@njutcm.edu.cn.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.
authors.forename: Ze-Xi
authors.initials: ZX
authors.lastname: Dong
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.
authors.forename: Peng-Xuan
authors.initials: PX
authors.lastname: Zhang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Gu
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Wu
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Yang
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, PR China. Electronic address: dja@njutcm.edu.cn.
authors.forename: Jin-Ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047310:Apigenin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001780:Blood Coagulation Tests; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D008745:Methylation; D015394:Molecular Structure; D016716:PC12 Cells; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D005343:Fibrinolytic Agents; D047310:Apigenin; D005340:Fibrinogen; D006861:Hydrogen Peroxide; C458179:scutellarein
keywords: Antioxidant; Metabolism; Methylation; Scutellarein; Scutellarin; Thrombin