A novel proton transfer salt of 2-amino-6-sulfamoylbenzothiazole and its metal complexes: the evaluation of their inhibition effects on human cytosolic carbonic anhydrases

J Enzyme Inhib Med Chem. 2017 Dec;32(1):231-239. doi: 10.1080/14756366.2016.1247058.


A novel proton transfer compound (SMHABT)+(HDPC)- (1) obtained from 2-amino-6-sulfamoylbenzothiazole (SMABT) and 2,6-pyridinedicarboxylic acid (H2DPC) and its Fe(III), Co(II), Ni(II) complexes (2-4), and Fe(II) complex of SMABT (5) have been prepared and characterized by spectroscopic techniques. Additionally, single crystal X-ray diffraction techniques were applied to complexes (2-4). All complexes (2-4) have distorted octahedral conformations and the structure of 5 might be proposed as octahedral according to spectral and analytical results. 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. The synthesized compounds have remarkable inhibitory activities on hCA I and hCA II. Especially, the inhibition potentials of the salt and the metal complexes (1-5) are comparable with AAZ. Inhibition data have been analyzed by using a one-way analysis of variance for multiple comparisons (p < .0001).

Keywords: 2,6-pyridinedicarboxylic acid; 2-amino-6-sulfamoylbenzothiazole; Carbonic anhydrase; metal complex; proton transfer; statistical analyses.

MeSH terms

  • Benzothiazoles / chemistry*
  • Benzothiazoles / pharmacology*
  • Carbon-13 Magnetic Resonance Spectroscopy
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / drug effects*
  • Crystallography, X-Ray
  • Cytosol / enzymology*
  • Humans
  • Metals / chemistry*
  • Protein Conformation
  • Proton Magnetic Resonance Spectroscopy
  • Protons
  • Spectrophotometry, Ultraviolet
  • Spectroscopy, Fourier Transform Infrared


  • Benzothiazoles
  • Carbonic Anhydrase Inhibitors
  • Metals
  • Protons
  • Carbonic Anhydrases

Grant support

This work was supported by the Dumlupinar University Research Fund [(grant No. 2014/18)].