Microwave-assisted synthesis and myorelaxant activity of 9-indolyl-1,8-acridinedione derivatives

Eur J Med Chem. 2014 Mar 21:75:258-66. doi: 10.1016/j.ejmech.2014.01.059. Epub 2014 Jan 31.

Abstract

In this study a microwave-assisted method was applied for the synthesis of novel 9-(substituted indolyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione derivatives. The structures of the compounds were confirmed by spectral methods including X-ray studies and elemental analysis. The Emax and pD2 values of the compounds and pinacidil were determined on noradrenaline precontracted tissues of isolated strips of rabbit gastric fundus smooth muscle. The obtained results indicated that some compounds and pinacidil produced concentration-dependent relaxation on the strips. The efficacy of compound 9 was higher than pinacidil. Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. Methyl substituents on the acridine backbone and bromine atom on the indole ring led to more active compounds.

Keywords: Acridinedione; Myorelaxant activity; Pinacidil; Potassium channel.

MeSH terms

  • Acridines / chemical synthesis
  • Acridines / chemistry*
  • Acridines / pharmacology*
  • Animals
  • Crystallography, X-Ray
  • Microwaves
  • Molecular Docking Simulation
  • Muscle Relaxation / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology*
  • Pinacidil / pharmacology
  • Potassium Channels / chemistry
  • Potassium Channels / metabolism
  • Rabbits

Substances

  • 1,8-acridinedione
  • Acridines
  • Potassium Channels
  • Pinacidil