Synthesis and Cytotoxicity Studies of Titanocene C Analogues

From the carbolithiation of 6- N , N -dimethylamino fulvene (3) and 2,4[bis( N , N -dimethylamino)methyl]- N -methylpyrrolyl lithium (2a) ,N -( N ′ , N ′ -dimethylaminomethyl)benzimidazolyl lithium (2b) , orp -( N , N -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 inN , N -dimethylamino-functionalised titanocenes 5a–c . When these titanocenes were tested against a pig kidney epithelial cell line (LLC-PK), theIC 50values obtained were of 23, and 52 μ M for titanocenes 5a and 5b , respectively. The most cytotoxic titanocene in this paper, 5c with anIC 50value of 13  μ M, was found to be approximately two times less cytotoxic than its analogue Titanocene C ( IC 50 = 5.5  μ M) and almost four times less cytotoxic than cisplatin, which showed anIC 50value of 3.3  μ M when tested on the LLC-PK cell line.