Synthesis, Characterization, and Assessment of Cytotoxic Properties of a Series of Titanocene Dichloride Derivatives

Abstract

A series of 15 water-soluble titanocene dichloride derivatives containing alkylammonium groups pendant to one (monocationic complexes) or both (dicationic complexes) cyclopentadienyl rings has been synthesized and characterized. The in vitro cytotoxicities of this small library of potential anticancer drugs have been assessed against human lung cancer (H209, A549, H209/CP) and ovarian cancer (A2780, A2780/CP) cell lines, and the results are compared with the cytotoxicities of both cisplatin (cis-PtCl2(NH3)2) and a clinical formulation of titanocene dichloride that is commonly used against cisplatin-resistant tumors. While none of the compounds exhibit potency greater than that of cisplatin, several are clearly superior to the clinical formulation. In particular dicationic complexes generally exhibit greater potency than do the corresponding monocationic analogues, and derivatives containing protonated piperidinyl rings exhibit greater potency than do compounds containing protonated 2-aminoethyl or 3-aminopropyl groups. Eight of the compounds, representing a wide range of potencies, were characterized crystallographically but no correlations between effectiveness and structures were obvious.