Synthesis and Cytotoxicity Studies of Titanocene C Analogues

From the carbolithiation of 6- [Formula: see text]-dimethylamino fulvene (3) and 2,4[bis([Formula: see text]-dimethylamino)methyl]- [Formula: see text]-methylpyrrolyl lithium (2a), [Formula: see text]-([Formula: see text]-dimethylaminomethyl)benzimidazolyl lithium (2b), or [Formula: see text]-([Formula: see text]-dimethylamino)methylphenyl lithium (2c), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl(4') resulting in [Formula: see text]-dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against a pig kidney epithelial cell line (LLC-PK), the [Formula: see text] values obtained were of 23, and 52 [Formula: see text] M for titanocenes 5a and 5b, respectively. The most cytotoxic titanocene in this paper, 5c with an [Formula: see text] value of 13 [Formula: see text] M, was found to be approximately two times less cytotoxic than its analogue Titanocene C ([Formula: see text] [Formula: see text] M) and almost four times less cytotoxic than cisplatin, which showed an [Formula: see text] value of 3.3 [Formula: see text] M when tested on the LLC-PK cell line.