title: Water-soluble Co(III) complexes of substituted phenanthrolines with cell selective anticancer activity.
abstract: Transition metal complexes with substituted phenanthrolines as ligands represent potential anticancer products without the drawbacks of platinum complexes that are currently marketed. Here, we report the synthesis and cell selective anticancer activity of five new water-soluble Co(III) complexes with methyl substituted phenanthroline ligands. The complexes were characterized by elemental analysis, NMR, FAB-mass spectrometry, FTIR, electronic spectroscopy, and single crystal X-ray diffraction. Possible interaction of these complexes with DNA was assessed by a combination of circular dichroism, UV-vis spectroscopy titration, and ethidium bromide displacement assay, and the results indicated that DNA interaction is weak for these complexes. Cellular uptake and cytotoxicity of complexes at low concentrations were assessed by flow cytometry on PC-3 cells, while their effect on intracellular mitochondrial function was measured by MTS assay on HeLa and PC-3 cell lines. These complexes showed selective cytotoxicity with a significantly higher effect on intracellular mitochondrial function in PC-3 cells than in HeLa cells. At low concentrations, complex 2 had the highest cytotoxic effect on PC-3 cells, inducing around 38% cell death, and the correlation of cytotoxicity of these complexes to their hydrophobicity indicates that an appropriate value of the hydrophobicity is essential for high antitumor activity.
authors.affiliation: Department of Chemistry, University of Basel , Klingelbergstrasse 80, 4056, Basel, Switzerland.
authors.forename: Sivaraman
authors.initials: S
authors.lastname: Jagadeesan
authors.forename: Vimalkumar
authors.initials: V
authors.lastname: Balasubramanian
authors.forename: Patric
authors.initials: P
authors.lastname: Baumann
authors.forename: Markus
authors.initials: M
authors.lastname: Neuburger
authors.forename: Daniel
authors.initials: D
authors.lastname: Häussinger
authors.forename: Cornelia G
authors.initials: CG
authors.lastname: Palivan
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002942:Circular Dichroism; D003035:Cobalt / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008928:Mitochondria / Q000187:drug effects; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010618:Phenanthrolines / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship; D014867:Water
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D010618:Phenanthrolines; D014867:Water; D003035:Cobalt; D004247:DNA