Imidazo[2,1-b]thiazole derivatives as new inhibitors of 15-lipoxygenase

Eur J Med Chem. 2014 Nov 24:87:759-64. doi: 10.1016/j.ejmech.2014.10.011. Epub 2014 Oct 6.

Abstract

A series of 3,6-diphenylimidazo[2,1-b]thiazol-5-amine derivatives was synthesized and evaluated as potential inhibitors of 15-lipoxygenase. Among the synthesized compounds, 5i bearing 2,4,4-trimethylpentan-2-yl pendent group was the most active compound, being two times more potent than reference drug quercetin. Also, the docking study revealed that 5i interacts properly with target enzyme 15-LOX and hydrophobic interactions have important role in the binding process. Besides, the protective effect of 5i against oxidative stress-induced cell death in differentiated PC12 cells was evaluated. The results showed that compound 5i significantly protected PC12 cells against H2O2-induced cell death at concentrations less than 10 μM.

Keywords: 15-Lipoxygenase; Docking study; Enzyme inhibitors; Imidazo[2,1-b]thiazole.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 15-Lipoxygenase / drug effects*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Lipoxygenase Inhibitors / chemistry
  • Lipoxygenase Inhibitors / pharmacology*
  • Magnetic Resonance Spectroscopy
  • Molecular Docking Simulation
  • PC12 Cells
  • Rats
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*

Substances

  • Imidazoles
  • Lipoxygenase Inhibitors
  • Thiazoles
  • imidazo(2,1-b)thiazole
  • Arachidonate 15-Lipoxygenase