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

Pampillon, C., Claffey, J., Strohfeldt, K. and Tacke, M. (2008) Synthesis and cytotoxicity studies of new dimethylamino-functionalised and aryl-substituted titanocene anti-cancer agents. European Journal of Medicinal Chemistry, 43 (1). pp. 122-128. ISSN 0223-5234 doi: 10.1016/j.ejmech.2007.02.011

Abstract/Summary

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 26 mu M 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 3.3 mu M, when tested on the LLC-PK cell line, but approximately 100 times better than titanocene dichloride. (C) 2007 Elsevier Masson SAS. All rights reserved.