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dc.contributor.authorTarushi, Alketa
dc.contributor.authorKakoulidou, Chrisoula
dc.contributor.authorRaptopoulou, Catherine P.
dc.contributor.authorPsycharis, Vassilis
dc.contributor.authorKessissoglou, Dimitris P.
dc.contributor.authorZoi, Ioanna
dc.contributor.authorPapadopoulos, Athanasios N.
dc.contributor.authorPsomas, George
dc.date.accessioned2017-05-22T17:51:50Z
dc.date.available2017-05-22T17:51:50Z
dc.date.issued2017-05
dc.identifier.citationZinc complexes of diflunisal: Synthesis, characterization, structure, antioxidant activity, and in vitro and in silico study of the interaction with DNA and albumins 2017, 170:85 Journal of Inorganic Biochemistryen
dc.identifier.issn01620134
dc.identifier.doi10.1016/j.jinorgbio.2017.02.010
dc.identifier.urihttp://hdl.handle.net/10150/623572
dc.description.abstractFrom the reaction of ZnCl2 with 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.
dc.language.isoenen
dc.publisherELSEVIER SCIENCE INCen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S016201341630407Xen
dc.rights© 2017 Elsevier Inc. All rights reserved.en
dc.subjectDiflunisalen
dc.subjectZinc complexesen
dc.subjectBiological activityen
dc.subjectInteraction with DNAen
dc.subjectMolecular dockingen
dc.titleZinc complexes of diflunisal: Synthesis, characterization, structure, antioxidant activity, and in vitro and in silico study of the interaction with DNA and albuminsen
dc.typeArticleen
dc.contributor.departmentDepartment of Chemistry and Biochemistry, University of Arizonaen
dc.identifier.journalJournal of Inorganic Biochemistryen
dc.description.note24 month embargo; Available online 12 February 2017en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal accepted manuscripten
html.description.abstractFrom the reaction of ZnCl2 with 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.


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