Abstract:

Aim – the search for biologically active compounds with diuretic and hypoglycemic action among 7-substituted of 3-benzyl-8-propylxanthines, which can be used for the treatment of pathologies of “metabolic syndrome”. Materials and methods. 30 new chemical compounds among derivatives of 7-substituted of 3-benzyl-8-propylxanthines by PASS prediction filter were chosen for diuretic and hypoglycemic activity researches. Diuretic, hypoglycemic activity and for the most active compounds – the acute toxicity were studied in vivo. The molecular docking, which is based on EADock DSS mechanism of the modulation displayed the interaction between some of functional groups inside discovered xanthine ligands and known receptors and enzymes presented in Ligand-protein Database of Swiss Institute of Bioinformatics. Results. It has been shown that synthesized compounds displayed strong diuretic and medium hypoglycemic activities. The molecular docking modulation (SwissDock) of interaction of xanthine derivatives hits with proposed receptors and enzymes revealed prospective of using 7-substituted of 3-benzyl-8-propylxanthines as potential drugs for treatment of metabolic syndrome pathologies. Conclusion. The diuretic activity of the new 23 compounds of 7-substituted of 3-benzyl-8-propylxanthines and hypoglycemic activity of the new 7 derivatives of 7-substituted of 3-benzyl-8-propylxanthines was studied. Results of performed investigation illustrate that 7-substituted of 3-benzyl-8-propylxanthines demonstrate biological activity comparable to standard drugs. We also proposed probable molecular targets for the most active compounds by molecular docking method. It was shown that derivatives of 7-substituted of 3-benzyl-8-propylxanthines can be used for metabolic syndrome disorders prevention.

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