Copper(II) interacting with the non-steroidal antiinflammatory drug flufenamic acid: Structure, antioxidant activity and binding to DNA and albumins

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• 作者：Charikleia Tolia^a ; Athanassios N. Papadopoulos^b ; Catherine P. Raptopoulou^c ; Vassilis Psycharis^c ; Claudio Garino^d ; Luca Salassa^e ; George Psomas^a ; ^{gepsomas@chem.auth.gr}
• 关键词：Copper complexes ; Non-steroidal antiinflammatory drugs ; Flufenamic acid ; Interaction with DNA ; Interaction with serum albumins ; Antioxidant activity
• 刊名：Journal of Inorganic Biochemistry
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：123
• 期：Complete
• 页码：53-65
• 全文大小：972 K

文摘

Copper(II) complexes with the non-steroidal antiinflammatory drug flufenamic acid (Hfluf) in the presence of N,N-dimethylformamide (DMF) or nitrogen donor heterocyclic ligands (2,2¡ä-bipyridylamine (bipyam), 1,10-phenanthroline (phen), 2,2¡ä-bipyridine (bipy) or pyridine (py)) have been synthesized and characterized. The crystal structures of [Cu₂(fluf)₄(DMF)₂], 1, and [Cu(fluf)(bipyam)Cl], 2, have been determined by X-ray crystallography. Density functional theory (DFT) (CAM-B3LYP/LANL2DZ/6-31G**) was employed to determine the structure of complex 2 and its analogues (complexes [Cu(fluf)(phen)Cl], 3, [Cu(fluf)(bipy)Cl], 4 and [Cu(fluf)₂(py)₂], 5). Time-dependent DFT calculations of doublet-doublet transitions show that the lowest-energy band in the absorption spectrum of 2-5 has a mixed d-d/LMCT character. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA with [Cu(fluf)(bipy)Cl] exhibiting the highest binding constant to CT DNA. The complexes can bind to CT DNA via intercalation as concluded by studying the cyclic voltammograms of the complexes in the presence of CT DNA solution and by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) have shown that the complexes can displace the DNA-bound EB suggesting strong competition with EB. Flufenamic acid and its Cu(II) complexes exhibit good binding affinity to human or bovine serum albumin protein with high binding constant values. All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase showing significant activity with [Cu(fluf)(phen)Cl] being the most active.