Synthesis and characterization of a novel amino salicylato salt and its Cu(II) complex and their inhibition studies on carbonic anhydrase isoenzymes

Abstract

A novel amino salicylato salt, 2-amino-6-methylpyridinium 2-hydroxy-5-sulfonatobenzoate (1), and its Cu(II) complex, 2-ammonio-6-methylpyridinium bis([mu(6)-5-sulfonatosalicylatoaquacopper(II)) (2), have been synthesized from free ligands, namely 5-sulfosalicylic acid (H(3)ssa) and 2-amino-6-methylpyridine (amp). Compounds 1 and 2 have been characterized by elemental, spectral (H-1 NMR, IR and UV-Vis) and thermal analyses. Additionally, magnetic measurements and the single crystal X-ray diffraction technique have been applied to compound 2. Compound 2 crystallizes in the triclinic P (1) over bar space group. In the symmetric unit, the Cu(II) ion exhibits a distorted square planar configuration, coordinated by two carboxylate oxygen atoms (O2 and O2(i)), one phenolic oxygen atom (01) of the ssa(3-) anion and a water molecule (O1w). The free ligands H3ssa and amp, and the products 1 and 2, and acetazolamide (AAZ) as a control compound have been also evaluated for their in vitro inhibitor effects on human carbonic anhydrase isoenzymes (hCA I and hCA II), purified from the erythrocyte cell by affinity chromatography for their hydratase and esterase activities. In relation to esterase activities, the inhibition equilibrium constants (Ki) have also been determined. A comparison of the inhibition studies of the newly synthesized compounds 1 and 2 with the parent compounds H(3)ssa and amp, and to AAZ, indicates that 1 and 2 have an effective inhibitory activity on hCA I and II, and can be used as potential inhibitors. (C) 2010 Elsevier Ltd. All rights reserved.