Manganese(II) Complexes with the Non-steroidal Anti-Inflammatory Drug Tolfenamic Acid: Structure and Biological Perspectives

Manganese­(II) complexes with the
non-steroidal anti-inflammatory
drug tolfenamic acid (Htolf)
with the nitrogen-donor heterocyclic ligands 1,10-phenanthroline (phen),
pyridine (py), or 2,2′-bipyridylamine (bipyam) and/or the oxygen-donor
ligands H2O or N,N-dimethylformamide
(DMF) have been synthesized and characterized. The crystal structures
of complexes [Mn­(tolf-O)­(tolf-O,O′)­(phen)­(H2O)],
[Mn2(μ2-tolf-O,O′)2(tolf-O,O′)2(bipyam)2], [Mn2(μ2-H2O)­(μ2-tolf-O,O′)2(tolf-O)2(py)4]·1.5MeOH·py, and [Mn­(μ2-tolf-O,O′)2(DMF)2]n have been determined by X-ray crystallography. The
interaction of the complexes with serum albumin proteins was investigated,
and relative high binding constant values were calculated. The ability
of the compounds to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2′-azinobis­(3-ethylbenzothiazoline-6-sulfonic
acid), and hydroxyl radicals was evaluated, and [Mn­(tolf)2(phen)­(H2O)] was the most active scavenger among the compounds.
The compounds have also exhibited noteworthy in vitro inhibitory activity against soybean lipoxygenase. UV titration studies
of the interaction of the complexes with calf-thymus (CT) DNA have
proved the binding to CT DNA with [Mn­(μ2-tolf)2(DMF)2]n exhibiting
the highest DNA-binding constant (Kb =
5.21 (±0.35) × 105 M–1). The
complexes bind to CT DNA probably via intercalation as suggested by
DNA-viscosity measurements and competitive studies with ethidium bromide
(EB), which revealed the ability of the complexes to displace the
DNA-bound EB.