title: DNA as a Target for Anticancer Phen-Imidazole Pd(II) Complexes.
abstract: Imidazole ring is a known structure in many natural or synthetic drug molecules and its metal complexes can interact with DNA and do the cleavage. Hence, to study the influence of the structure and size of the ligand on biological behavior of metal complexes, two water-soluble Pd(II) complexes of phen and FIP ligands (where phen is 1,10-phenanthroline and FIP is 2-(Furan-2-yl)-1H-Imidazo[4,5-f][1, 10]phenanthroline) with the formula of [Pd(phen)(FIP)](NO3)2and [Pd(FIP)2]Cl2, that were activated against chronic myelogenous leukemia cell line, K562, were selected. Also, the interaction of these anticancer Pd(II) complexes with highly polymerized calf thymus DNA was extensively studied by means of electronic absorption, fluorescence, and circular dichroism in Tris-buffer. The results showed that the binding was positive cooperation and [Pd(phen)(FIP)](NO3)2(Kf= 127 M-1G = 1.2) exhibited higher binding constant and number of binding sites than [Pd(FIP)2]Cl2(Kf= 13 M-1G = 1.03) upon binding to DNA. The fluorescence data indicates that quenching effect for [Pd(phen)(FIP)](NO3)2(KSV= 58 mM-1) was higher than [Pd(FIP)2]Cl2(KSV= 12 mM-1). Also, [Pd(FIP)2]Cl2interacts with ethidium bromide-DNA, as non-competitive inhibition, and can bind to DNA via groove binding and [Pd(phen)(FIP)](NO3)2can intercalate in DNA. These results were confirmed by circular dichroism spectra. Docking data revealed that longer complexes have higher interaction energy and bind to DNA via groove binding. Graphical Abstract Two anticancer Pd(II) complexes of imidazole derivative have been synthesized and interacted with calf thymus DNA. Modes of binding have been studied by electronic absorption, fluorescence, and CD measurements. [Pd(FIP)2]Cl2can bind to DNA via groove binding while intercalation mode of binding is observed for [Pd(phen)(FIP)](NO3)2.
authors.affiliation: Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Heydari
authors.affiliation: Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran. eslami_moghadam@ccerci.ac.ir.
authors.forename: Mahboube Eslami
authors.initials: ME
authors.lastname: Moghadam
authors.affiliation: Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran.
authors.forename: AliAkbar
authors.initials: A
authors.lastname: Tarlani
authors.affiliation: Chemistry & Chemical Engineering Research Center of Iran, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Farhangian
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D002413:Cations, Divalent; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D004996:Ethidium / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D020014:K562 Cells; D008024:Ligands; D062105:Molecular Docking Simulation; D010165:Palladium / Q000737:chemistry*; D010618:Phenanthrolines / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D002413:Cations, Divalent; D056831:Coordination Complexes; D005663:Furans; D007093:Imidazoles; D007364:Intercalating Agents; D008024:Ligands; D010618:Phenanthrolines; D010165:Palladium; D004247:DNA; C427203:calf thymus DNA; D004996:Ethidium; C025205:1,10-phenanthroline
keywords: Circular dichroism; DNA binding; Docking; Fluorescence; Imidazole derivative; Palladium (II) complexes