title: Picolinate ruthenium(II)-arene complex with in vitro antiproliferative and antimetastatic properties: comparison to a series of ruthenium(II)-arene complexes with similar structure.
abstract: In our previous study, ruthenium(II)-p-cymene complexes of general formula [(η(6)-p-cymene)Ru(L)Cl2], L: 3-acetylpyridine (1), 2-amino-5-chloropyridine (2); and [(η(6)-p-cymene)Ru(HL)Cl], HL: 2,3-pyridinedicarboxylic acid (3), 2,4-pyridinedicarboxylic acid (4), revealed low antiproliferative activity, except complex [(η(6)-p-cymene)RuCl(picolinic acid)]·H(2)O (5) which exhibited IC(50) around 80 μM. In this study we further investigated in vitro potential of antimetastatic action of ruthenium complexes on HeLa and two endothelial cell lines. Comparison of structure and activity of five complexes indicated heterogenic mode of activity, with regard to the potential of antimetastatic and antiproliferative effect. Replacement of substituted pyridine ligand with picolinic acid (complex 5) around Ru(II) center contributed to complex cytotoxicity and ruthenium DNA binding affinity. Analysis of ruthenium(II) accumulation in DNA and protein fractions of HeLa cells, using ICP-OES revealed significantly higher content of complex 5 in DNA fraction in comparison to the other tested compounds. It also altered cell cycle progression, affected expression of DNA repair enzymes ERCC1 and MSH2, and showed enhanced activity in combination with 3-aminobenzamide. Regardless of their effect on cell growth, Ru(II) complexes exerted antimetastatic effect on several tumor cell lines in vitro, achieved mostly by the effect on cell adhesion, migration and angiogenesis, while picolinate ruthenium(II)-arene additionally exerted inhibitory effect on extracellular matrix degradation.
authors.affiliation: Institute for Oncology and Radiology of Serbia, Belgrade, Serbia.
authors.forename: Nevenka
authors.initials: N
authors.lastname: Gligorijević
authors.forename: Sandra
authors.initials: S
authors.lastname: Aranđelović
authors.forename: Lana
authors.initials: L
authors.lastname: Filipović
authors.forename: Ksenija
authors.initials: K
authors.lastname: Jakovljević
authors.forename: Radmila
authors.initials: R
authors.lastname: Janković
authors.forename: Sanja
authors.initials: S
authors.lastname: Grgurić-Šipka
authors.forename: Ivanka
authors.initials: I
authors.lastname: Ivanović
authors.forename: Siniša
authors.initials: S
authors.lastname: Radulović
authors.forename: Zivoslav Lj
authors.initials: ZLj
authors.lastname: Tešić
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010848:Picolinic Acids / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D017975:Ruthenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010848:Picolinic Acids; D017975:Ruthenium Compounds; D012428:Ruthenium; C030614:picolinic acid