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


YENİKAYA C., SARI M. , BÜLBÜL M., İLKİMEN H., Celik H., BÜYÜKGÜNGÖR O.

BIOORGANIC & MEDICINAL CHEMISTRY, vol.18, no.2, pp.930-938, 2010 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 18 Issue: 2
  • Publication Date: 2010
  • Doi Number: 10.1016/j.bmc.2009.11.031
  • Title of Journal : BIOORGANIC & MEDICINAL CHEMISTRY
  • Page Numbers: pp.930-938
  • Keywords: 2,4-Dichloro-5-sulfamoylbenzoic acid, Inhibition, 2-Amino-3-methylpyridine, Proton transfer, Zn(II) complex, Glaucoma, Crystal structure, CARBONIC-ANHYDRASE INHIBITORS, ISOFORM-II, SULFONAMIDE DERIVATIVES, CRYSTAL-STRUCTURE, ISOZYME-XIV, IN-VIVO, IX, ZINC(II), ANTICANCER, ESTERASE

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 (H-1 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 IC50 values of products 1 and 2 for hydratase activity are 0.26 and 0.13 mu M for hCA I and 0.30 and 0.15 mu M for hCA II, respectively. The IC50 values of the same inhibitors for esterase activity are 0.32 and 0.045 mu M for hCA I and 0.29 and 0.23 mu M for hCA II, respectively. In relation to esterase activities, the inhibition equilibrium constants (K-i) were also determined and found 0.25 and 0.058 mu M on hCA I and 0.22 and 0.24 mu M 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. (C) 2009 Elsevier Ltd. All rights reserved.