Cobalt(II) complexes with non-steroidal anti-inflammatory drug tolfenamic acid: Structure and biological evaluation

Abstract

Cobalt(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid in the presence or absence of nitrogen-donor heterocyclic ligands (2,2′-bipyridine, 1,10-phenanthroline, 2,2′-bipyridylamine or pyridine) have been synthesized and characterized with physicochemical and spectroscopic techniques. The deprotonated tolfenamato ligands are coordinated to Co(II) ion through carboxylato oxygen atoms. The crystal structures of complexes [bis(2,2′-bipyridine) bis(methanol)bis(tolfenamato)cobalt(II)] 2 and [bis(2,2′-bipyridylamine)bis(tolfenamato)cobalt(II)] 4 have been determined by X-ray crystallography. UV studies of the interaction of the complexes with calf-thymus DNA (CT DNA) have shown that the complexes can bind to CT DNA and [bis(methanol)(1,10-phenanthroline)bis(tolfenamato)cobalt(II)] exhibits the highest binding constant to CT DNA. The cyclic voltammograms of the complexes recorded in DMSO solution and in the presence of CT DNA in 1/2 DMSO/buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. Tolfenamic acid and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.