Synthesis of tetraketones and determination their biological activity

Tetraketones are cyclic compounds, synthetised from dimedone (cyclohexane-1,3-dione) and benyaldehydes via Knoevenegel condenzation and Michaels addition, by principles of green chemistry with catalyst. They are very interesting because they have wide range of biological activity such as antioxidant activity and inhibitory activity against enzymes lopoxygenase, tyrosinase and protein kinase. It has been determined that have strong cytotoxic as well as antimicrobial activity. The primary aim of this study was to synthesize new series of tetraketones and to relate their biologcal activity to chemical structure. Results showed that all synthesized tetraketones have different antioxidant activity, compounds with hydroxyl group in the structure were responsible for the strongest activity, also we found the correlation between the number of gropus and  activity. Compound with ortho hydroxyl groups in the phenyl ring proved to be strongest antioxidant and has stronger activity than vitamin C. They also act as strong inhibitors of the enzyme tyrosinase, the most potent compound is with ortho hydroxyl groups in the ring, at the concentration of 512 μM inhibits tyrosinase activity of 86,9%, other compounds show weaker inhibitory activity. Stronger antimicrobial activity have compounds with lipophilic aromatic substituents, SAR analysis suported by SwissADME parameters indicated that the observed antimicrobial activity deepends on balanced relationship between lipophilicity, polarity and diffusion properties of the molecules. There is a correlation between biological activity and structure of tetraketones, compounds with polar funcional groups such as hydroxy, methoxy and ethoxy have stronger antioxidant activity and  inhibitory activity against tyrosinase; compounds with lipophilic substituents such as fluorine, chlorine and trifluoromethly have better antimicrobial activity.