Novel achiral indole-substituted titanocenes: Synthesis and preliminary cytotoxicity studies

A series of eight new titanocene dichloride derivatives has been synthesised and characterized. Four compounds from the series are lypophilic indole-functionalised titanocenes and four are hydrochloride salts of their dimethylaminomethyl-functionalised counterparts, which are water soluble. The compounds were tested for their in vitro cytotoxicities against the human kidney cancer cell line CAKI-1 and their results are compared with previously synthesised structural analogues. Surprisingly, two of the compounds showed no activity against the CAKI-1 cell line; however six compounds exhibited medium to high potency with IC50 values as low as 7.0 μM. These six complexes were tested further on this cell line using the co-solvent Soluphor P, which has been shown to improve both solubility and cytotoxicity of similar complexes. One of the compounds carrying a N-methylindole-substituent was obtained in the form of single crystals and allowed for the characterisation by X-ray crystallography; the compound crystallised in the space group P21/n (#14) with four molecules present in the monoclinic unit cell.

Graphical abstractEight new achiral indole-functionalised titanocene dichloride complexes were synthesised through hydridolithiation of the appropriately substituted fulvenes. The synthesis of these compounds is reported alongside with the structural discussion of one derivative. Additionally, these compounds were tested for their in vitro anticancer properties on the renal cancer CAKI-1 cell line.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► Eight indole-functionalised titanocenes were synthesised. ► One crystal structure is reported. ► All derivatives were tested for cytotoxicity against renal cancer cells.