title: Zinc complexes of diflunisal: Synthesis, characterization, structure, antioxidant activity, and in vitro and in silico study of the interaction with DNA and albumins.
abstract: From the reaction of ZnCl2with the non-steroidal anti-inflammatory drug diflunisal (Hdifl), complex [Zn(difl-O)2(MeOH)4], 1 was formed, while in the presence of a N,N'-donor heterocyclic ligand 2,2'-bipyridylamine (bipyam), 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) and 2,2'-dipyridylketone oxime (Hpko), the complexes [Zn(difl-O,O')2(bipyam)], 2, [Zn(difl-O,O')2(bipy)], 3, [Zn(difl-O,O')2(phen)], 4 and [Zn(difl-O)2(Hpko)2], 5 were isolated, respectively. The complexes were characterized by physicochemical and spectroscopic techniques and the crystal structures of complexes 2, 3 and 5 were determined by X-ray crystallography. The ability of the complexes to scavenge 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals and to inhibit soybean lipoxygenase was studied and the complexes were more active than free Hdifl. The interaction of the complexes with serum albumins was monitored by fluorescence emission spectroscopy and the corresponding binding constants were calculated. UV-vis spectroscopy, viscosity measurements and fluorescence emission spectroscopy for the competitive studies of the complexes with ethidium bromide were employed to investigate the interaction of the complexes with calf-thymus DNA and revealed intercalation as the most possible DNA-binding mode. Computational techniques were used to identify possible binding sites of albumins and DNA, and determine the druggability of human and bovine serum albumins with the five novel complexes. The majority of the complexes are stronger binders than the free Hdifl. This is the first study incorporating experimental and computational results to explore the binding activity of metal-NSAID complexes with DNA and serum albumins, suggesting their application as potential metallodrugs.
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, P.O. Box 135, GR-54124 Thessaloniki, Greece.
authors.forename: Alketa
authors.initials: A
authors.lastname: Tarushi
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, P.O. Box 135, GR-54124 Thessaloniki, Greece.
authors.forename: Chrisoula
authors.initials: C
authors.lastname: Kakoulidou
authors.affiliation: Institute of Nanoscience and Nanotechnology, NCSR "Demokritos", GR-15310 Aghia Paraskevi, Attikis, Greece.
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Raptopoulou
authors.affiliation: Institute of Nanoscience and Nanotechnology, NCSR "Demokritos", GR-15310 Aghia Paraskevi, Attikis, Greece.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Psycharis
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, P.O. Box 135, GR-54124 Thessaloniki, Greece.
authors.forename: Dimitris P
authors.initials: DP
authors.lastname: Kessissoglou
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, USA.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Zoi
authors.affiliation: Department of Nutrition and Dietetics, Faculty of Food Technology and Nutrition, Alexandrion Technological Educational Institution, Sindos, Thessaloniki, Greece.
authors.forename: Athanasios N
authors.initials: AN
authors.lastname: Papadopoulos
authors.affiliation: Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, P.O. Box 135, GR-54124 Thessaloniki, Greece. Electronic address: gepsomas@chem.auth.gr.
authors.forename: George
authors.initials: G
authors.lastname: Psomas
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D004061:Diflunisal / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D012710:Serum Albumin, Bovine; D004061:Diflunisal; D004247:DNA; D015032:Zinc
keywords: Biological activity; Diflunisal; Interaction with DNA; Interaction with albumins; Molecular docking; Zinc complexes