Synthesis and cytotoxicity studies of new dimethylamino-functionalised and aryl-substituted titanocene anti-cancer agents.

Abstract

From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated aryl species [p-N,N-dimethylanilinyl lithium, p-anisyl lithium and 4-lithio-benzo[1.3]dioxole (2a-c)], the corresponding lithium cyclopentadienide intermediates 4a-c were formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised and aryl-substituted titanocenes 5a-c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 54, 45 and 26microM for titanocenes 5a, b and c, respectively. The most cytotoxic titanocene in this paper, 5c is approximately 10 times less cytotoxic than cis-platin, which showed an IC50 value of 3.3microM, when tested on the LLC-PK cell line, but approximately 100 times better than titanocene dichloride.

• Authors: Clara Pampillón, James Claffey, Katja Strohfeldt, Matthias Tacke
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 43 Issue 1 Pg. 122-8 (Jan 2008) ISSN: 0223-5234 [Print] France
• PMID: 17412456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Dimethylamines
• Organometallic Compounds
• metallocene
• titanocene
• dimethylamine

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology, toxicity)
• Cell Line
• Cell Survival (drug effects)
• Crystallography, X-Ray
• Dimethylamines (chemistry)
• Inhibitory Concentration 50
• Organometallic Compounds (chemical synthesis, chemistry, pharmacology, toxicity)
• Quantum Theory
• Solubility