Synthesis, characterization and antiglaucoma activity of a novel proton transfer compound and a mixed-ligand Zn(II) complex

Bioorg Med Chem. 2010 Jan 15;18(2):930-8. doi: 10.1016/j.bmc.2009.11.031. Epub 2009 Nov 20.

Abstract

A novel proton transfer compound, pyridin-2-ylmethanaminium 2,4-dichloro-5-sulfamoylbenzoate (1), and a mixed-ligand Zn(II) complex, bis(2,4-dichloro-5-sulfamoylbenzoate)(2-aminomethylpyridine)aquazinc(II) monohydrate (2), have been synthesized from the same free ligands, which are 2,4-dichloro-5-sulfamoylbenzoic acid (Hsba) and 2-aminomethylpyridine (amp). They have been characterized by elemental, spectral ((1)H NMR, IR and UV-vis.) and thermal analyses. Additionally, magnetic measurement and single crystal X-ray diffraction technique were applied to compound 2. In the complex, Zn(II) ion exhibits a distorted octahedral configuration coordinated by O1 and O1(i) atoms of two mono dentante sba anions and N1, N2, N2(i) atoms of bidentante amp anion and a water molecule (O1w). The free ligands Hsba and amp, and the products 1 and 2, and acetazolamide (AAZ) as the control compound, were also evaluated for their in vitro inhibitor effects on human Carbonic Anhydrase isoenzymes (hCA I and hCA II) purified from erythrocyte cell by affinity chromatography for their hydratase and esterase activities. The IC(50) values of products 1 and 2 for hydratase activity are 0.26 and 0.13microM for hCA I and 0.30 and 0.15microM for hCA II, respectively. The IC(50) values of the same inhibitors for esterase activity are 0.32 and 0.045microM for hCA I and 0.29 and 0.23microM for hCA II, respectively. In relation to esterase activities, the inhibition equilibrium constants (K(i)) were also determined and found 0.25 and 0.058microM on hCA I and 0.22 and 0.24microM on hCA II for 1 and 2, respectively. The comparison of the inhibition studies of newly synthesized compounds 1 and 2 to parent compounds Hsba and amp and to AAZ indicated that 1 and 2 have effective inhibitory activity on hCA I and II, and might be used potential inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase I / antagonists & inhibitors
  • Carbonic Anhydrase I / isolation & purification
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / antagonists & inhibitors
  • Carbonic Anhydrase II / isolation & purification
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Crystallography, X-Ray
  • Erythrocytes / enzymology
  • Glaucoma / drug therapy*
  • Glaucoma / enzymology
  • Glaucoma / metabolism
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Protons*
  • Spectroscopy, Fourier Transform Infrared
  • Structure-Activity Relationship
  • Temperature
  • Zinc / chemistry*

Substances

  • Carbonic Anhydrase Inhibitors
  • Ligands
  • Organometallic Compounds
  • Protons
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • Zinc