title: Assessment of DNA-binding affinity of cholinesterase reactivators and electrophoretic determination of their effect on topoisomerase I and II activity.
abstract: In this paper, we describe the biochemical properties and biological activity of a series of cholinesterase reactivators (symmetrical bisquaternary xylene-linked compounds, K106-K114) with ctDNA. The interaction of the studied derivatives with ctDNA was investigated using UV-Vis, fluorescence, CD and LD spectrometry, and electrophoretic and viscometric methods. The binding constants K were estimated to be in the range 1.05 × 10(5)-5.14 × 10(6) M(-1) and the percentage of hypochromism was found to be 10.64-19.28% (from UV-Vis titration). The used methods indicate that the studied samples are groove binders. Electrophoretic methods proved that the studied compounds clearly influence calf thymus Topo I (at 5 μM concentration, except for compounds K107, K111 and K114 which were effective at higher concentrations) and human Topo II (K110 partially inhibited Topo II effects even at 5 μM concentration) activity.
authors.affiliation: Institute of Chemistry, Department of Biochemistry, Faculty of Science, P. J. Safarik University, Moyzesova 11, 040 01 Kosice, Slovak Republic. maria.kozurkova@upjs.sk and Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Janockova
authors.affiliation: Institute of Chemistry, Department of Biochemistry, Faculty of Science, P. J. Safarik University, Moyzesova 11, 040 01 Kosice, Slovak Republic. maria.kozurkova@upjs.sk.
authors.forename: E
authors.initials: E
authors.lastname: Zilecka
authors.affiliation: Department of Biophysics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Kasparkova
authors.affiliation: Department of Biophysics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech Republic.
authors.forename: V
authors.initials: V
authors.lastname: Brabec
authors.affiliation: Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Soukup
authors.affiliation: Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Kuca
authors.affiliation: Institute of Chemistry, Department of Biochemistry, Faculty of Science, P. J. Safarik University, Moyzesova 11, 040 01 Kosice, Slovak Republic. maria.kozurkova@upjs.sk and Biomedical Research Center, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Kozurkova
mesh_terms: D002801:Cholinesterase Reactivators / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D011485:Protein Binding; D013057:Spectrum Analysis; D014783:Viscosity
chemical_list: D002801:Cholinesterase Reactivators; D004247:DNA; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II