Synthesis of scutellarein derivatives to increase biological activity and water solubility

Bioorg Med Chem. 2015 Nov 1;23(21):6875-84. doi: 10.1016/j.bmc.2015.09.047. Epub 2015 Oct 1.

Abstract

In order to improve the biological activity and water solubility of scutellarin (1), some derivatives of its main metabolite (scutellarein) were designed and synthesized. All the compounds were tested for their thrombin inhibition activity through the analyzation of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) 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, their water solubility were also assessed by ultraviolet (UV) spectrophotometer. The results showed that compound 8b demonstrated stronger anticoagulant and antioxidant activity, better water solubility compared with scutellarein (2), which warrants it as a promising agent for the treatment of ischemic cerebrovascular disease.

Keywords: Antioxidant; Scutellarein; Scutellarin; Solubility; Thrombin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / chemical synthesis
  • Anticoagulants / chemistry
  • Anticoagulants / pharmacology
  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Apigenin / chemical synthesis
  • Apigenin / chemistry*
  • Apigenin / pharmacology
  • Fibrinogen / metabolism
  • Hydrogen Peroxide / toxicity
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Prothrombin Time
  • Rats
  • Solubility
  • Thrombin / antagonists & inhibitors
  • Thrombin / metabolism
  • Thrombin Time

Substances

  • Anticoagulants
  • Antioxidants
  • Apigenin
  • Fibrinogen
  • Hydrogen Peroxide
  • Thrombin
  • scutellarein