Synthesis and characterization of complexes of a novel proton transfer salt and their inhibition studies on carbonic anhydrase isoenzymes

J Enzyme Inhib Med Chem. 2015 Apr;30(2):195-203. doi: 10.3109/14756366.2014.908290. Epub 2014 Apr 23.

Abstract

A novel proton transfer compound (HClABT)(+)(HDPC.H2DPC)(-) (1) and its Fe(III), Co(II), Ni(II) and two different Cu(II) complexes (2-6) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to all complexes. All compounds, including acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibition effects on human hCA I and hCA II for their hydratase and esterase activities. Although there is no inhibition for hydratase activities, all compounds have inhibited the esterase activities of hCA I and II. The comparison of the inhibition studies of 1-6 to parent compounds, ClABT and H2DPC, indicates that 1-6 have superior inhibitory effects. The inhibition effects of 2-6 are also compared to the inhibitory properties of the simple metal complexes of ClABT and H2DPC, revealing an improved transfection profile. Data have been analysed by using a one-way analysis of variance for multiple comparisons.

Keywords: 2,6-pyridinedicarboxylic acid; 2-Amino-6-chlorobenzothiazole; carbonic anhydrase; proton transfer; statistical analyses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase I / antagonists & inhibitors*
  • Carbonic Anhydrase I / isolation & purification
  • Carbonic Anhydrase II / antagonists & inhibitors*
  • Carbonic Anhydrase II / isolation & purification
  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Erythrocytes / enzymology
  • Humans
  • Isoenzymes
  • Molecular Structure
  • Picolinic Acids
  • Protons*
  • Pyridines / chemistry*
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Carbonic Anhydrase Inhibitors
  • Coordination Complexes
  • Isoenzymes
  • Picolinic Acids
  • Protons
  • Pyridines
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • dipicolinic acid