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Information × Registration Number 0213U004064, 0110U001010 , R & D reports Title Pathogenetic substantiation for the prospectivity of the foundation of antidiabetic compounds with pleotropic effects on the base of original 1,3-diazaheterocycles derivatives popup.stage_title Head Poltorack Victoria Vitaliyivna, Доктор медичних наук Registration Date 31-01-2013 Organization Ukrainian Research Institute of Endocrine Diseases Pharmacotherapy popup.description2 The objects of the study were rabbits, rats, mice, heterocyclic compounds with 1,3-diazafragments. Purpose of the study was the identification among the heterocyclic derivatives with 1,3-diazafragments new compounds with glucose-lowering, anti-atherogenic and anti-inflammatory effects, which increase the body's sensitivity to insulin, and the ability of pancreatic beta-cells and hepatocytes to survive. Methods of the study - organic synthesis, physical and chemical analysis, biochemical, pharmacological and molecular-biological. A number of new compounds with established structure of thiazolidinone and azoloazine classes was synthesized. The method of molecular docking showed that some of them have the energy of interaction with 11beta-hydroxysteroid dehydrogenase 1 receptor at the level of reference product, which indicates whether the direct pharmacological testing of the synthesized derivatives as inhibitors of the enzyme. According to the primary pharmacological screenings to determine the antioxidant and hypoglycaemic activities was established promising of the substances AD-0109, AD-1208, AD-1408, AD-0409, AD-0111, AD-0407, 2506, 2418, 2419 and 2420 of a number of heterocyclic compounds with 1,3 diazafragments as potential anti-diabetic agents. An evaluation of the acute toxicity of the compounds AD-1408, 2506, 2418 and 2419 found that they are practically non-toxic substances. New ways of modeling the major pathogenic mechanisms of type 2 diabetes mellitus in rabbits and rats using dexamethasone were proposed. On the model of type 2 diabetes mellitus in rabbits was verified the ability of substances AD-1408 and 2418 to improve insulin sensitivity, glucose and lipid metabolism parameters, as well as reducing the intensity of lipid peroxidation in the serum. Studies of the effect of AD-1408, 2506, 2418 and 2419 compounds in rats with type 2 diabetes mellitus of different origins revealed the ability of these compounds to reduce the dysglycemia, dyslipidemia, insulin resistance and oxidative stress parameters. In models of type 2 diabetes mellitus in rabbits and rats from apoptosis parameter studies proved the existence of a positive effect of oral administration of the AD-1408 and 2506 compounds for a total survival of the liver and pancreas cells. Areas of use - pharmaceutical industry. Product Description popup.authors Бородіна Вікторія Василівна Бурма Тетяна Юхимівна Вакула Володимир Миколайович Гладких Олександр Іванович Завадська Наталія Володимирівна Карножицька Тетяна Михайлівна Карпова Тетяна Олексіївна Кравченко Світлана Вікторівна Красова Наталія Сергіївна Кудря Марія Яківна Ліпсон Вікторія Вікторівна Лещенко Жанна Анатоліївна Нікішина Людмила Євгеніївна Полторак Вікторія Віталіївна Редькін Руслан Григорович Сидорова Ірина Василівна Сова Олександр Миколайович Тижненко Тетяна Василівна Устенко Нонна Василівна Яременко Федір Георгійович popup.nrat_date 2020-04-02 Close