The novel ketoprofen amides--synthesis and biological evaluation as antioxidants, lipoxygenase inhibitors and cytostatic agents

Chem Biol Drug Des. 2010 Jun;75(6):641-52. doi: 10.1111/j.1747-0285.2010.00963.x. Epub 2010 Mar 19.

Abstract

The novel amides of ketoprofen and its reduced derivatives (5a-f, 4a-n, 6a-g) with aromatic and cycloalkyl amines or hydroxylamines were prepared and screened for their reducing and cytostatic activity as well as for their ability to inhibit soybean lipoxygenase and lipid peroxidation. 1,1-Diphenyl-picrylhydrazyl test for reducing ability revealed that ketoprofen amides were more potent antioxidants than the amides of the reduced ketoprofen derivatives. The most active compound was benzhydryl ketoprofen amide 5f. Lipoxygenase inhibition of the tested compounds varied from strong to very weak. The most potent compound was benzhydryl derivative 6f (IC(50) = 20.5 mum). Aromatic and cycloalkyl amides 4 and 5 were more potent lipoxygenase inhibitors than derivatives with carboxylic group. Aromatic amides of series 4 and 5 showed excellent lipid peroxidation inhibition (92.2-99.9%). On the other hand, the most pronounced cytostatic activity was exerted by O-benzyl derivative 4i, although in general all tested reduced and non-reduced lipophilic derivatives showed similar activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / chemical synthesis*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Cell Line, Tumor
  • Cytostatic Agents / chemical synthesis*
  • Cytostatic Agents / chemistry
  • Cytostatic Agents / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Ketoprofen / chemical synthesis
  • Ketoprofen / chemistry*
  • Ketoprofen / pharmacology
  • Lipoxygenase / chemistry*
  • Lipoxygenase / metabolism
  • Lipoxygenase Inhibitors / chemical synthesis*
  • Lipoxygenase Inhibitors / chemistry
  • Lipoxygenase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Antioxidants
  • Cytostatic Agents
  • Lipoxygenase Inhibitors
  • Ketoprofen
  • Lipoxygenase