ИСТИНА

The presentation will focus on a novel approach to design hybrid organic and organometallic physiollogically active compounds based on computer-aided design, new synthetic approaches and extensive biological screenings. This study is focused on the construction of hybrid compounds with dual modes of action possessing 2,6-dialkylphenol group as a α-tocopherol mimetic and metal center. The hybrid compounds might show either prooxidative activity or antioxidative activity. The presence of metal atom allows extensive modification including coordination to the targeted specific groups to control and tune toxicity-activity profiles. The synthesis and anti/prooxidant activity and cytotoxicity studies of novel hybrid compounds are presented and discussed. The biological activity has been studied in in vitro, ex vivo, in vivo experiments in lipid peroxidation and mitochondria-associated processes, by using neurons, liver homogenates and in enzymatic reactions (xanthine oxidase, lipoxygenase, glutathione reductase, thioredoxin reductase). Thus, we can conclude that the combination of two physiologically active moieties in a complex molecule is a promising approach to find the novel hybrid therapeutic agents with opposed biological mode of action