Serum transferrin is responsible for distributing Fe(III) to cells throughout the body. It has been postulated as the hydrolysis stabilizer of compounds of Ti(IV), which are known to be highly unstable in aqueous solution, by effectively chelating the metal ion and transporting it to cells by means via the same endocytotic route as Fe(III). Although this mechanism suggests a promising new anticancer drug design based on the cellular delivery of cytotoxic Ti(IV), efforts to develop a drug sustained in transferrin does not generate results favoring the improvement of the cytotoxic activity of Ti(IV) on cancer cells. Instead, it is proposed to design compounds of Ti(IV) using mimetic transferrin ligands to facilitate not only the stabilization and delivery of Ti(IV), but also to ensure the reduction of intracellular levels of Fe(III), which is detrimental to cancer cells because of their high requirement for Fe(III). deferasirox, a molecule designed to reduce excess of Fe(III) levels in pharmacological uses has been proposed as a potential chemical transferrin mimetic ligand. It stabilizes Ti(IV) but because it has a stronger affinity for Fe(III), it would be able to exchange Ti(IV) for capture of Fe(III) intracellularly. This study focuses on the synthesis of Ti(IV)-deferasirox complexes, the characterization of their structures in solution and solid state, and the kinetic studies of deferasirox metal exchange between Ti(IV) and Fe(III). The <i>in vitro </i>evaluation of the cytotoxicity of Ti(IV)-deferasirox complexes against A549 (lung carcinoma) and MRC5 (lung epithelial cells healthy) cell lines suggest a high activity comparable to other Ti(IV) complexes currently in development and even more activity versus the metal-free ligand.

Evaluating the potential of deferasirox, a commercial chemical transferrin mimetic, in Ti(IV) anticancer drug design

251st National Meeting (2016)

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