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) × 10(5) 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.
Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki , GR-54124 Thessaloniki, Greece.
Marianthi
M
Zampakou
Natalia
N
Rizeq
Vassilis
V
Tangoulis
Athanasios N
AN
Papadopoulos
Franc
F
Perdih
Iztok
I
Turel
George
G
Psomas
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry*; D002417:Cattle; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004247:DNA; D004996:Ethidium / Q000737:chemistry; D008345:Manganese / Q000737:chemistry*; D015394:Molecular Structure; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D056831:Coordination Complexes; D062367:ortho-Aminobenzoates; D012710:Serum Albumin, Bovine; C009500:tolfenamic acid; D008345:Manganese; D004247:DNA; C427203:calf thymus DNA; D004996:Ethidium