Synthesis and cytotoxicity studies of new (dimethylamino)-functionalised and 7-azaindole-substituted 'titanocene' anticancer agents (7-azaindole=1H-pyrrolo[2,3-b]pyridine)

摘要

From the carbolithiation of 1-(cyclopenta-2,4-dien-1-ylidene)-N,N-diniethylmethanamine (=6-(dimethylamino)fulvene; 3) and different lithiated azaindoles 2 (1-methyl-7-azaindol-2-yl, 1-[(diethylamino)methyl]-7-azaindol-2-yl, and 1-(methoxymethyl)-7-azaindol-2-yl), the corresponding lithium cyclopentadienide intermediates 4a-4c were formed (7-azaindole = 1H-pyrrolo[2,3-b]pyridine). The latter underwent a transmetallation reaction with TiCl4 resulting in the (dimethylamino)-functionalised 'titanocenes' 5a-5c. When the 'titanocenes' 5a-5c were tested against LLC-PK cells, the IC50 values obtained were of 8.8, 12, and 87 mu pm, respectively. The most cytotoxic 'titanocene' 5a, with an IC50 value of 8.8 mu m is nearly as cytotoxic as cis-platin, which showed an IC50 Value of 3.3 mu m when tested on the epithelial pig kidney LLC-PK cell line, and ca. 200 times better than 'titanocene dichloride' itself.