There are several studies where titanium (Ti) is used for the development of potential anticancer agents. Cancer cells are known for their uncontrolled cell proliferation; therefore, they require a high amount of the iron-containing ribonucleotide reductase (RNR) enzyme to catalyze the conversion of ribonucleotides to deoxyribonucleotides (a reduction process), which are the building blocks of DNA. The enzyme serves as an attractive target for anti-cancer therapy. We are targeting the class I RNR enzyme (which exists in all eukaryotes and some prokaryotes) via Ti(IV) complexes of iron chelator ligands, e.g. HBED[N,N′-di(o-hydroxybenzyl)ethylene-diamine-N,N′-diacetic acid] and deferasirox. The study will reveal the possible cause of cytotoxicity of Ti(IV) complexes on cancer cells by analyzing the chelation of Fe(III) by iron chelators and the interaction of Ti(IV) with the suspected enzyme RNR I by electron paramagnetic resonance (EPR) spectroscopy. To catalyze the reduction process, RNR I, which contains two Fe(III) in its β2 subunit undergoes oxidation and generates a tyrosyl radical. Our preliminary results indicate a significant reduction in the signal associated with the tyrosyl radical (signal at g=2), as well as increased level of high-spin Fe(III) complexes (signal at g=4) in the whole cell EPR analysis when the Jurkat cells were incubated with the Ti(IV) complexes having ligands with iron chelating features. The signal reduction is due to the loss of enzyme activity and the increased level of high-spin Fe(III) complexes indicates the formation of new high-spin Fe(III) species. The requirements of enzyme inactivation and the formation of new Fe(III) complexes can be accomplished when the redox-inactive metal Ti(IV) is complexed with iron chelating ligands. The hypothesis is to serve Ti(IV) complexes as the ‘effective inhibitors’ of the RNR I via chelating its iron, because enzyme activation requires oxidation of Fe(II) to Fe(III), however, oxidation cannot be possible for the redox inert Ti(IV).<br/>

Ribonucleotide reductase enzyme a target for titanium complexes: A strategy to cure cancer

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.