title: Design, synthesis, and biological evaluation of andrographolide derivatives as potent hepatoprotective agents.
abstract: Poor water solubility limits the clinical use of andrographolide and its derivatives. In an attempt to develop potent hepatoprotective drugs, a strategy was proposed to improve the aqueous solubility of andrographolide. Ten andrographolide derivatives were designed, synthesized, evaluated for aqueous solubility and in vivo hepatoprotective activity against CCl4 -induced liver injury in mice. As expected, the aqueous solubility of synthetic derivatives was effectively improved. All compounds demonstrated the effect of different degrees in improving the liver enzyme (ALT and AST) activity, especially the most promising compound 9d significantly improved liver enzyme activity, with high potency to be a new lead.
authors.affiliation: State Key Laboratory of Natural Medicines, Centre of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China; School of Pharmaceutical Science, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Tang
authors.forename: Guolong
authors.initials: G
authors.lastname: Gu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhu
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006842:Hydrocarbons, Brominated; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020011:Protective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: C000592740:3-oxo-19-O-(2-(4-hydroxypiperidino)acetyl)dehydroandrographolide; D004224:Diterpenes; D006842:Hydrocarbons, Brominated; D010880:Piperidines; D020011:Protective Agents; D014867:Water; C030419:andrographolide; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C031387:carbon tetrabromide
keywords: andrographolide derivatives; aqueous solubility; hepatoprotective activity; synthesis