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.
Highlights
The prevalence of the metabolic syndrome (MS) is the actual problem among adult population of the developed countries [1]
Molecular docking revealed the formation of three hydrophobic bindings between phenylthiosemicarbazone of 3-benzyl-8-propylxanthynyl-7 acetic acid and glycine 47, isoleucine 46 and 218, which correlates with the inhibition data of enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD 11B1) [17]
We achieved the result of molecular docking, which indicate the presence of interactions between hydrazide 3-benzyl-8-propylxanthinyl-7 acetic acid and phenylalanine 1276, which blocks interaction of A1-receptor [19] with targeted mediator – adenosine
Summary
The prevalence of the metabolic syndrome (MS) is the actual problem among adult population of the developed countries [1]. In general MS is associated with increasing of everyday calories intake, sedentary lifestyle, which is based on the improvement access to quality food and the progress of the technology in which human is engaged on intelligent levels of management [2]. According to the WHO data [3] of post-industrial countries the frequency of MS is 10–20 % among 30 years and older population, in the USA – 34 % (44 % for those who are (2019), «EUREKA: Health Sciences» Number 5 older 50 years). Survey of American Diabetes Association shows that current syndrome demonstrates impetuous growth of appearance between teenagers and young people [4].
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