Research article summary (published 28 Feb 2006):

Antitumour activity of [1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride in xenografted Ehrlich's ascites tumour.

Full Abstract

The effects of a new titanocene compound with an ansa ligand in the cyclopentadienyl rings, the 1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride (TITANOCENE X), on the growth and differentiation of granulocyte-macrophage progenitor cells [colony-forming unit-granulocyte-macrophage (CFU-GM)] and Natural killer (NK) cell activity in Ehrlich's ascites tumour (EAT)-bearing mice were studied. Myelosuppression concomitant with increased numbers of spleen CFU-GM was observed in tumour-bearing mice. Treatment of these animals with TITANOCENE X (2.5-50 mg/kg/day) produced an increase in myelopoiesis, in a dose-dependent manner, and reduced spleen colony formation. In addition, the treatment of EAT-bearing mice with 3 doses of 20 or 50 mg/kg TITANOCENE X restored to normal values the reduced Natural killer cell function observed during tumour growth. In parallel, TITANOCENE X prolonged, in a dose-dependent manner, the survival of mice inoculated with Ehrlich's ascites tumour. The highest dose of 50 mg/kg prolonged in 50% the survival time of EAT-bearing mice, compared to non-treated tumour-bearing controls. In comparison with previous results from our laboratory addressing the effects of titanocenes on haematopoiesis, we observed with TITANOCENE X a similar effective profile as for bis(cyclopentadienyl) dithiocyanate titanium(IV), being both less effective than di(cyclopentadienyl) dichloro titanium(IV), since the latter not only prolonged, but also increased the rate of survival. These differences in efficacy may be due to the nature of the ansa-cyclopentadienyl ligand used in TITANOCENE X, since the C2 bridge between the two cyclopentadienyl groups will increase the hydrolytic stability by an organometallic chelate effect. Also, the introduction of two dimethylamino substituents increases the water solubility of TITANOCENE X when compared to titanocene dichloride itself.

Author information

Author/s: Valadares, Marize C (MC); Ramos, Aline L (AL); Rehmann, Franz-Josef K (FJ); Sweeney, Nigel J (NJ); Strohfeldt, Katja (K); Tacke, Matthias (M); Queiroz, Mary L S (ML);

Affiliation: Faculdade de Farmácia, Universidade Federal de Goiás, UFG, Goiânia, GO, Brazil.

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't

Journal: European journal of pharmacology (Eur J Pharmacol), published in Netherlands. (Language: eng)

Reference: 2006-Mar; vol 534 (issue 1-3) : pp 264-70

Dates: Created 2006/03/13; Completed 2006/06/07; Revised 2006/11/15;

PMID: 16513106, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Antineoplastic Agents - pharmacology; therapeutic use Carcinoma, Ehrlich Tumor - drug therapy; immunology; pathology Cell Proliferation Colony-Forming Units Assay Dose-Response Relationship, Drug Hematopoietic Stem Cells - drug effects; pathology

Killer Cells, Natural - drug effects; immunology Male Mice Mice, Inbred BALB C Myelopoiesis - drug effects Neoplasm Transplantation Organometallic Compounds - pharmacology; therapeutic use

Associated Chemicals: (1,2-di(cyclopentadienyl)-1,2-di(4-N,N-dimethylaminophenyl)ethanediyl)titanium dichloride (0) ; Antineoplastic Agents (0) ; Organometallic Compounds (0)

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