title: Activity of [1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride against tumor colony-forming units.
abstract: [1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride is a newly synthesized transition metal-based anti-cancer drug. We studied the anti-tumor activity of this drug (final concentrations: 25, 250 and 2,500 micromol/l) against freshly explanted human tumors, using an in vitro soft agar cloning system. A total of eight tumor samples were evaluated using 1-h exposures. Additionally, the breast carcinoma cell line MCF-7 was examined with regard to sensitivity. The tested compound was markedly active against one renal cancer sample, whereas other renal tumors were resistant. Concentration-dependent anti-tumor activity was demonstrated for all samples except for melanoma. At concentrations of 250 micromol/l or less, the compound was less active than cisplatin or equally active at 0.2 microg/ml, whereas at 2,500 micromol/l it showed a significant cytotoxic activity against a wide spectrum of tumor types. The highest activity was observed against renal carcinomas (three of three tumor specimens inhibited at 2,500 micromol/l). Sensitivity was also highly remarkable in the breast cancer cell line MCF-7 inhibited in a range of 25-2,500 micromol/l, whereas melanoma cells seemed to be profoundly resistant. Further clinical development of this drug appears warranted because of the broad cytotoxic activity shown.
authors.affiliation: Allgemeines Krankenhaus St Georg, Hamburg, Germany. tian64@gmx.de
authors.forename: Olaf
authors.initials: O
authors.lastname: Oberschmidt
authors.forename: Axel-R
authors.initials: AR
authors.lastname: Hanauske
authors.forename: Franz-Josef K
authors.initials: FJ
authors.lastname: Rehmann
authors.forename: Katja
authors.initials: K
authors.lastname: Strohfeldt
authors.forename: Nigel
authors.initials: N
authors.lastname: Sweeney
authors.forename: Matthias
authors.initials: M
authors.lastname: Tacke
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000627:therapeutic use*; D014410:Tumor Stem Cell Assay
chemical_list: C507876:(1,2-di(cyclopentadienyl)-1,2-di(4-N,N-dimethylaminophenyl)ethanediyl)titanium dichloride; D000970:Antineoplastic Agents; D009942:Organometallic Compounds