Mannich bases of scutellarein as thrombin-inhibitors: design, synthesis, biological activity and solubility

Bioorg Med Chem. 2012 Dec 15;20(24):6919-23. doi: 10.1016/j.bmc.2012.10.015. Epub 2012 Oct 23.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Apigenin / chemical synthesis
  • Apigenin / chemistry*
  • Apigenin / pharmacology*
  • Drug Design
  • Humans
  • Mannich Bases / cerebrospinal fluid
  • Mannich Bases / chemistry
  • Mannich Bases / pharmacology
  • Models, Molecular
  • Solubility
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors*

Substances

  • Antioxidants
  • Mannich Bases
  • Apigenin
  • Thrombin
  • scutellarein