Ti(IV) ANTI-CANCER COMPLEXES BASED ON SALAN LIGANDS: COVALENT AND NON COVALENT COMBINATIONS WITH OTHER ACTIVE SITES

The significant drawbacks of cisplatin, namely its high toxicity and development of drug-resistance, initiated an extensive search for other metals that can lead to anti-cancer activity. Ti(IV) complexes showed promising cytotoxic activity, and two Ti(IV) based complexes reached clinical trials. Nevertheless, these complexes have failed the trials due to instability in aqueous environment. Our group designed a new family of anti-cancer Ti(IV) complexes based on phenolato ligands, which showed high cytotoxic activity toward numerous cancer cell lines and enhanced stability in aqueous environment.

Combination therapy is very common in clinical treatment of cancer. By combining two drugs or more, the doses that are required to reach the desired effect are reduced, and consequently, side effects and toxicity are reduced as well.

Herein, combination of salan Ti(IV) complexes with other active species are presented. Non-covalent combinations of salan Ti(IV) complexes and cisplatin showed mostly synergistic behavior, which is medicinally valuable.¹ Moreover, efforts are made to covalently combine salan Ti(IV) complexes with cisplatin, and to compare to the non-covalent combinations. Covalent combinations of salan Ti(IV) complexes with sex hormones that feature membrane recognition may enhance the selectivity of the complexes to particular cell types. Achievements in these directions will be discussed.

(1) Ganot, N.; Redko, B.; Gellerman, G.; Tshuva, E. Y. Rsc Adv. 2015, 5 (11), 7874–7879.