Synthesis and study of new paramagnetic and diamagnetic verapamil derivatives

Bioorg Med Chem. 2010 Apr 15;18(8):2954-63. doi: 10.1016/j.bmc.2010.02.040. Epub 2010 Feb 25.

Abstract

New derivatives of verapamil (1) modified with nitroxides and their precursors were synthesized and screened for reactive oxygen species (ROS)-scavenging activities. The basic structure was modified by changing the nitrile group to an amide or the methyl substituent on tertiary nitrogen with nitroxides and their reduced forms (hydroxylamine and secondary amines). Among the new verapamil derivatives compound 16B [Mohan, I. K.; Kahn, M.; Wisel, S.; Selvendiran, K.; Sridhar, A.; Carnes, C.A.; Bognár, B.; Kálai, T.; Hideg, K.; Kuppusamy, P. Am. J. Physiol. Heart Circ. Physiol.2009, 296, 140], modified with hydroxylamine salt of 2,2,6,6-tetramethyl-1,2,3,6-tetrahydropyridine-1-yloxyl proved to be the best ROS scavenger in vitro and protected HSMC and CHO cells against H(2)O(2) induced damage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cardiotonic Agents / chemical synthesis*
  • Cardiotonic Agents / chemistry
  • Cardiotonic Agents / pharmacology
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Electron Spin Resonance Spectroscopy
  • Free Radical Scavengers / chemical synthesis*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Magnetics*
  • Verapamil / analogs & derivatives
  • Verapamil / chemical synthesis
  • Verapamil / chemistry*
  • Verapamil / pharmacology

Substances

  • 1-hydroxy-2,2,6,6-tetramethyl-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid-(2-(3,4-dimethoxyphenyl)-5-(2-(3,4-dimethoxyphenyl)ethyl)methylamino)-2-isopropyl-pentylamide
  • Cardiotonic Agents
  • Free Radical Scavengers
  • Hydrogen Peroxide
  • Verapamil