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(μ 6-5-sulfonatosalicylatoaquacopper(II)) ( 2), have been synthesized from free ligands, namely 5-sulfosalicylic acid (H 3ssa) and 2-amino-6-methylpyridine (amp). Compounds 1 and 2 have been characterized by elemental, spectral ( 1H 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 ¯ 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 (O1) of the ssa 3− anion and a water molecule (O1w). The free ligands H 3ssa 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 3ssa 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.