title: Refolding and unfolding of CT-DNA by newly designed Pd(II) complexes. Their synthesis, characterization and antitumor effects.
abstract: New antitumor Pd(II) compounds derived from oxygen donor ligands salicylate (SA) (1) and sulfosalicylate (SSA) (2) dianions and nitrogen donor heterocyclic ligand 2,2'-bipyridine (bpy) were synthesized and characterized by elemental analysis, UV-Vis, FT-IR,1H NMR and conductivity measurements. The complexes evaluated for their cytotoxicity effects towards cancer cell line of K562 using MTT assay. They are more cytotoxic than cisplatin. The dependence of their interaction modes with CT-DNA on concentration of the compounds has been discovered in this work. CT-DNA binding studies of these complexes have been investigated by UV-Vis absorption, ethidium bromide (EB) displacement, fluorescence, circular dichroism and gel electrophoresis techniques. The apparent binding constants (Kapp) has been obtained 3.9 and 10.9×104M-1at lower concentration range and 1.03 and 1.59×104M-1at higher concentration range for complexes (1) and (2), respectively. These complexes effectively interact with CT-DNA in the order of (2)>(1). Fluorescence studies exhibited that the complexes quench CT-DNA-EB by simultaneous static and dynamic quenching processes. The calculated binding (Kapp, kq, KSV, n) and thermodynamic (ΔG°, ΔH°, ΔS°) parameters revealed that hydrophobic, van der Waals forces and hydrogen binding holds the Pd(II) complexes in the CT-DNA grooves. Gel electrophoresis supports the spectroscopic experiments.
authors.affiliation: Department of Chemistry, University of Sistan and Baluchestan, Zahedan 009854, Iran.
authors.forename: Mahin
authors.initials: M
authors.lastname: Dustkami
authors.affiliation: Department of Chemistry, University of Sistan and Baluchestan, Zahedan 009854, Iran. Electronic address: hmtorshizi@hamoon.usb.ac.ir.
authors.forename: Hassan
authors.initials: H
authors.lastname: Mansouri-Torshizi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D020014:K562 Cells; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010165:Palladium / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010165:Palladium; D004247:DNA; C427203:calf thymus DNA
keywords: Cytotoxicity; DNA-binding; Palladium complexes; Salicylate and Sulfosalicylate