Аннотация:Metal-based drugs represent a relevant sector of the pharmaceutical market with potential development in the treatment of incurable diseases. There is an urgent need for the discovery of new drugs with novel modes of biological action, because several diseases develop resistances to known drugs. Metal compounds (metal-based drugs) might offer biological and chemical diversity that is distinct from that of organic substances. It has become increasingly apparent that metal-based pharmaceuticals can play a crucial role in oncology, treatment of metabolism- and genetic disorders, cardiovascular disease, gene therapy, inflammation, stroke, diabetes, malaria, and neurological disease. The goal of medicinal chemists is to create new inorganic/organometallic molecules as drug candidates. We will discuss the need for rationalization of the investigational approaches available to create hybrid metal-based drugs. 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. Our study is focused on a novel approach to design hybrid metal-based physiologically active compounds with opposed modes of action – prooxidant metal center and antioxidant 2,6-dialkylphenol group. The synthesis and anti/prooxidant activity and 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. The multifactor antiproliferative and antioxidative activities assay of novel compounds has been performed by using DPPH, CUPRAC-tests, and enzymatic methods (lipoxygenase, gluthathione reductase, thioredoxine reductase, tubulin); ex vivo lipid peroxidation in mitochondria isolated from rat brain and liver. The in vivo study was performed for the hit compounds.
