title: Palladium(II) complexes with N-heteroaromatic bidentate hydrazone ligands: the effect of the chelate ring size and lipophilicity on in vitro cytotoxic activity.
abstract: Novel Pd(II) complex with N-heteroaromatic Schiff base ligand, derived from 8-quinolinecarboxaldehyde (q8a) and ethyl hydrazinoacetate (haOEt), was synthesized and characterized by analytical and spectroscopy methods. The structure of novel complex, as well as structures of its quinoline and pyridine analogues, was optimized by density functional theory calculations, and theoretical data show good agreement with experimental results. A cytotoxic action of the complexes was evaluated on cultures of human promyelocytic leukemia (HL-60), human glioma (U251), rat glioma (C6), and mouse fibrosarcoma (L929) cell lines. Among investigated compounds, only complexes with quinoline-based ligands reduce the cell numbers in a dose-dependent manner in investigated cell lines. The observed cytotoxic effect of two isomeric quinoline-based complexes is predominantly mediated through the induction of apoptotic cell death in HL-60 cell line. The cytotoxicity of most efficient novel Pd(II) complex is comparable to the activity of cisplatin, in all cell lines investigated.
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11000, Belgrade, Serbia.
authors.forename: Nenad
authors.initials: N
authors.lastname: Filipović
authors.forename: Sonja
authors.initials: S
authors.lastname: Grubišić
authors.forename: Maja
authors.initials: M
authors.lastname: Jovanović
authors.forename: Marija
authors.initials: M
authors.lastname: Dulović
authors.forename: Ivanka
authors.initials: I
authors.lastname: Marković
authors.forename: Olivera
authors.initials: O
authors.lastname: Klisurić
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Marinković
authors.forename: Dragana
authors.initials: D
authors.lastname: Mitić
authors.forename: Katarina
authors.initials: K
authors.lastname: Anđelković
authors.forename: Tamara
authors.initials: T
authors.lastname: Todorović
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D018922:HL-60 Cells; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D051379:Mice; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry*; D051381:Rats; D012545:Schiff Bases / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D002614:Chelating Agents; D056831:Coordination Complexes; D006835:Hydrazones; D008024:Ligands; D012545:Schiff Bases; D010165:Palladium; D020169:Caspases
keywords: X-ray crystallography; apoptosis; biological screening; chemical structure; palladium(II) complexes