Synthesis and Cytotoxicity Studies of Titanocene C Analogues

Abstract

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) ' or p -( 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 in N , N -dimethylamino-functionalised titanocenes 5a–c . When these titanocenes were tested against a pig kidney epithelial cell line (LLC-PK), the IC 50 values obtained were of 23, and 52 μ M for titanocenes 5a and 5b , respectively. The most cytotoxic titanocene in this paper, 5c with an IC 50 value 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 an IC 50 value of 3.3 μ M when tested on the LLC-PK cell line.