Titanium (IV) Citrate Compounds as Cytotoxic Agents
Insitute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
Cisplatin is a well-known platinum based chemotherapeutic drug; authorized for use in 1978, it shows high anti-tumor activity against testicular and ovarian cancers, yet exhibits severe side effects.
Other metals are studied as alternatives for anticancer applications, including titanium. Titanium based coordination complexes are promising candidates because titanium is a biocompatible, non-toxic metal.
Indeed, titanium based coordination complexes have shown cytotoxicity with markedly reduced side effects. In particular, titanocene dichloride and budotitane are titanium compounds that reached clinical trials due to high cytotoxicity against various types of cancer with mild side effects. However, poor water insolubility and instability against hydrolysis were limiting factors. Strongly bound chelating ligands were shown to improve water stability while enabling high and selective anticancer activity in vitro and in vivo. Nevertheless, bulky ligands used in titanium compounds often inhibited cell penetration due to steric effects.
Other metals are studied as alternatives for anticancer applications, including titanium. Titanium based coordination complexes are promising candidates because titanium is a biocompatible, non-toxic metal.
Indeed, titanium based coordination complexes have shown cytotoxicity with markedly reduced side effects. In particular, titanocene dichloride and budotitane are titanium compounds that reached clinical trials due to high cytotoxicity against various types of cancer with mild side effects. However, poor water insolubility and instability against hydrolysis were limiting factors. Strongly bound chelating ligands were shown to improve water stability while enabling high and selective anticancer activity in vitro and in vivo. Nevertheless, bulky ligands used in titanium compounds often inhibited cell penetration due to steric effects.
Citrate is a physiological ligand and a strong chelating agent, allowing the synthesis of titanium compounds with hydrolytic stability, high water solubility and improved cell penetration. Additionally, recent studies have implied its possible participation in the titanium(IV) cellular interactions. Therefore, herein we studied citrate titanium(IV) complexes and analyzed their biological reactivity. We present cytotoxic activity of two titanium (IV) citrate complexes against HT-29 human colon cancer cells, one of which exhibits a novel structure.
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