ИСТИНА

Platinum (II) drugs, such as cisplatin are in wide clinical use in antitumor therapy. However, platinum compounds possess a number of crucial drawbacks, such as high overall toxicity and acquired resistance [1]. One of the approaches to overcome those drawbacks is development of platinum (IV) prodrugs. Upon oxidation, platinum (II) square-planar complex becomes a six-coordinate octahedral, with the addition of two ligands in axial position. Platinum (IV) complexes are kinetically more inert than their platinum (II) precursors, consequently, the unwanted reactions are minimized which leads to reduced side-effects and overall toxicity. The prodrugs are able to reduce after the tumor cell penetration, releasing the cytotoxic platinum (II) complex and axial ligands. Also, the addition of bioactive molecules as axial ligands allows to create a multiple action prodrugs [2]. We have developed new platinum (IV) prodrugs with axial ligands based on 2-thioimidazolin-4-one, which chelates Cu ions in cells. Cu plays vital role in cancer progression and it is reported that tissue and serum from cancer patients have increased Cu level [3]. A combination of platinum therapeutic agents with copper chelators leads to increase in anti-cancer therapy efficiency [4]. As a result, the developed platinum (IV) prodrugs are potentially more effective and less toxic to healthy tissue.