title: Mannich bases of scutellarein as thrombin-inhibitors: design, synthesis, biological activity and solubility.
abstract: Two series of 8-aminomethylated derivatives were prepared by Mannich reaction of scutellarein (2) with appropriate aliphatic amines, alicyclic amines and formaldehyde. All the compounds were tested for their thrombin inhibition activity through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The antioxidant activities of these target products were assessed by 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay method and the solubility were assessed by ultraviolet (UV). The results showed that morpholinyl aminomethylene substituent derivative (3d) demonstrated stronger anticoagulant activity, better water solubility and good antioxidant activity compared with scutellarein (2), which warrants further development as a agent for ischemic cerebrovascular disease treatment.
authors.affiliation: Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210046, China.
authors.forename: Nian-Guang
authors.initials: NG
authors.lastname: Li
authors.forename: Shu-Lin
authors.initials: SL
authors.lastname: Song
authors.forename: Min-Zhe
authors.initials: MZ
authors.lastname: Shen
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Tang
authors.forename: Zhi-Hao
authors.initials: ZH
authors.lastname: Shi
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.forename: Qian-Ping
authors.initials: QP
authors.lastname: Shi
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Fu
authors.forename: Jian-Ao
authors.initials: JA
authors.lastname: Duan
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D047310:Apigenin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008352:Mannich Bases / Q000134:cerebrospinal fluid / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D012995:Solubility; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D000975:Antioxidants; D008352:Mannich Bases; D047310:Apigenin; D013917:Thrombin; C458179:scutellarein