Antitumour activity of [1,2-di(cyclopentadienyl)-1,2-di(p-N,N-dimethylaminophenyl)-ethanediyl] titanium dichloride in xenografted Ehrlich's ascites tumour

Substituted titanocenes induce caspase-dependent apoptosis in human epidermoid carcinoma cells in vitro and exhibit antitumour activity in vivo

“…We have shown that one member from this series, Titanocene X is significantly more effective than titanium dichloride and exhibits potent cytotoxic effect on kidney carcinoma cells and is cytotoxic to cisplatin-resistant human ovarian carcinoma (Kelter et al, 2005). The antitumour potential of novel titanocenes was further demonstrated in freshly explanted human cervical carcinoma cells and kidney cells (Oberschmidt et al, 2005), xenografted Caki-1-bearing mice (Fichtner et al, 2006), xenografted Ehrlich's ascites tumours (Valadares et al, 2006) and MCF-7 xenografted mouse model of breast cancer (Beckhove et al, 2007). The dose-dependent effects observed in these in vivo models of human disease demonstrate the lack of general toxicity exerted by highly substituted titanocenes in tumour cells and suggest a tumourspecific effect.…”

“…It was found that the highly substituted titanocenes are as effective as cisplatin at inducing cell death against a broad range of human tumours, and in some cases, titanocenes displayed greater cytotoxicity than cisplatin. Titanocenes significantly reduce growth of ex vivo tumour explants (Oberschmidt et al, 2005) and reduce tumour growth in vivo (Fichtner et al, 2006;Valadares et al, 2006;Beckhove et al, 2007). Collectively, these reports suggest the potential of highly substituted titanocenes as novel anticancer agents in single or combination treatment regimens and for treatment of cisplatin-resistant tumours.…”

Glycol Methyl Ether and Glycol Amine Substituted Titanocenes as Antitumor Agents

“…[24] Furthermore, very successful animal studies with the use of titanocene Y on Caki-1 tumor-bearing mice and xenograft Ehrlich's ascites tumor in mice were performed. [25,26] The main idea behind the research presented in this paper was to convert the methoxy group of titanocene Y, our most cytotoxic titanocene, into a glycol methyl ether or glycol amine side chain in order to improve the cytotoxicity and availability in the cell. Within this paper, we present the synthetic possibilities and limits of introducing a glycol methyl ether or a glycol amine group in all three mentioned classes of titanocenes and comparing the antiproliferative effects of the new synthesised titanocenes.…”

The synthesis and cytotoxic evaluation of a series of benzodioxole substituted titanocenes

“…Preclinical trials using xenografted Caki-1 tumors and xenografted Ehrlich's ascites tumor in mice treated with X and Y have been recently reported and show an inhibition of tumour growth and tolerable sideeffects. 28,29 In this paper, we present the synthesis and preliminary cytotoxic evaluation of a series of titanocenes: an open benzyl dioxole-substituted titanocene, an ansa-titanocene with benzodioxole groups which are part of a chelate system and a highly substituted titanocene which contains two benzodioxole groups attached to each cyclopentadienyl ring. It was of interest to synthesize this class of titanocenes to see if inclusion of benzodioxole rings on the titanocene moiety would increase cytotoxicity, as it is similar to the methoxy functionality seen in Titanocene Y.…”