Review Article
Giuseppe Palma, Massimilian
Abstract
The discovery of cis-platin in the treatment of cancer there has been a considerable exploration on the antitumoral activity of other transition metal complexes. One of the main problems about the application of transition metal complexes for chemotherapy is their potential toxicity. Recently the attention has been focused on titanium based complexes, which could have significant potential effect against solid tumor. The advantage of Ti (IV) complexes is their relative biological compatibility, which mostly leads to mild and revisable side effects. However, the hydrolytic instability of known Ti(IV) complexes and formation of different species upon water addition makes their therapeutic application problematic, and raises a strong interest in the development of relatively stable Ti(IV) complexes with well defined hydrolytic behavior that demonstrate appreciable cytotoxic activity. Strong ligand binding is also of interest to avoid complete ligand stripping by transferrin, so that the ligand may be used as a target for structure–activity relationship investigations. Titanocene dichloride (Cp2TiCl2) shows an average antiproliferative activity in vitro and promising result in vivo. Recent work has been performed in developing therapeutic analogues of Cp2TiCl2 by varying the central metal, the labile ligands (Cl) and the biscyclopentadienyl moiety. In particular, small changes to the Cp ligand can strongly affect the hydrolytic stability and water solubility properties of the metallocenes and have an impact on the cytotoxic activity. In this review we want summarize the importance of different organo-mettalic compounds in cancer therapy with focus on possible structure modification.