ИСТИНА

The field of biological inorganic chemistry has grown consistently during the past 50 years. The description of the cell life needs not only the knowledge of its genome and proteome, but also of the location of the metal ions and their different complex species in the subcellular compartments, that is of metallome. The main goal of BIC is to understand the metalloprotein’s function and mechanism of activity and then design small molecule compounds (1) to confirm mechanism, (2) extend the catalytic activity for industrial purposes. On the other hand, it has become increasingly apparent that metal-based pharmaceuticals can play a prominent role in areas outside of imaging and oncology, including in those associated with the diagnosis and treatment of metabolism- and genetic disorders, cardiovascular disease, gene therapy, inflammation, stroke, diabetes, malaria, and neurological disease. We will discuss the need for rationalization of the investigational approaches available to create metallodrugs. Our key approaches were (1) to maintain the interaction with the target, and (2) to keep the balance between the antitumor potency and general toxicity. Scheme illustrates our two approaches: (1) modification of the known organic drug moiety as a delivery vector by introducing a metal atom for better targeting and efficacy (approach I); (2) modification of the known metal containing compound with proved pharmacological efficacy by introducing the protective groups for attenuation of general toxicity (approach II). Our study is focused on a design of polyfunctional metal-based physiollogically active compounds with opposed modes of action – prooxidant metal center and antioxidant 2,6-dialkylphenol group. The synthesis and anti/prooxidant activity and in vitro and in vivo cytotoxicity studies of novel organometallic/coordination compounds based on either biogenic metals (Fe, Mn, Co, Cu, Zn, Ni) or exogenic metals (Sn, Au,) are presented and discussed.