title: Titanium(IV) complexes: cytotoxicity and cellular uptake of titanium(IV) complexes on caco-2 cell line.
abstract: Replacement of the ancillary ligand in titanocene dichloride by amino acids provides titanocene species with high water solubility. As part of our research efforts in the area of titanium-based antitumor agents, we have investigated the cytotoxic activity of Cp(2)TiCl(2) and three water soluble titanocene-amino acid complexes - [Cp(2)Ti(aa)(2)]Cl(2) (aa=L-cysteine, L-methionine, and D-penicillamine) and one water soluble coordination compound, [Ti(4)(maltolato)(8)(micro-O)(4)] on the human colon adenocarcinoma cell line, Caco-2. At pH of 7.4 all titanocene species decompose extensively while [Ti(4)(maltolato)(8)(micro-O)(4)] is stable for over seven days. In terms of cytotoxicity, the [Cp(2)Ti(aa)(2)]Cl(2) and [Ti(4)(maltolato)(8)(micro-O)(4)] complexes exhibited slightly higher toxicity than titanocene dichloride at 24h, but at 72h titanocene dichloride and [Ti(4)(maltolato)(8)(micro-O)(4)] have higher cytotoxic activity. Cellular titanium uptake was quantified at various time intervals to investigate the possible relationship between Ti uptake and cellular toxicity. Results indicated that there was not a clear relationship between Ti uptake and cytotoxicity. A structure-activity relationship is discussed.
authors.affiliation: University of Puerto Rico, Department of Chemistry, Mayaguez,, Puerto Rico.
authors.forename: Ramón
authors.initials: R
authors.lastname: Hernández
authors.forename: Janet
authors.initials: J
authors.lastname: Méndez
authors.forename: José
authors.initials: J
authors.lastname: Lamboy
authors.forename: Madeline
authors.initials: M
authors.lastname: Torres
authors.forename: Féliz R
authors.initials: FR
authors.lastname: Román
authors.forename: Enrique
authors.initials: E
authors.lastname: Meléndez
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000633:toxicity*; D001667:Binding, Competitive / Q000187:drug effects; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004996:Ethidium / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000378:metabolism / Q000633:toxicity*; D013054:Spectrophotometry, Atomic; D017550:Spectroscopy, Fourier Transform Infrared; D014025:Titanium / Q000378:metabolism / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D004247:DNA; D014025:Titanium; D004996:Ethidium; C020528:titanocene dichloride