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Introduction. In the modern world people are exposed to the influence of adverse psychological and physical factors, escalating in intensity. The search for new pharmacodynamic effects of [1,3,5]-thiadiazine derivatives designated by significant biological activity of these compounds is an essential issue.Aim. To research adaptogenic activity of tetrahydropyrido[2,1-b][1,3,5]thiadiazine derivatives using a modified Porsolt Forced Swim Test.Materials and methods. Four substances from the group of 3-R-8-aryl-6-oxo-3,4,7,8-tetrahydro-2H,6Hpyrido[2,1-b][1,3,5]thiadiazine-9-carbonitriles were selected for the research. Rats were divided into a control group, 5 reference groups (amitriptyline, caffeine, thiotriazolin, thiocetam, ginseng) and 4 experimental groups according to the number of the studied original tetrahydropyrido[2,1-b][1,3,5] thiadiazine derivatives.Results. Intragastric injection of substance 2 for 5 days in the modified forced swim test (forced swimming with freight) increased work capacity and endurance of the rats by 103.42% as opposed to the initial results. The detected adaptogenic activity of this tetrahydropyrido[2,1-b][1,3,5]thiadiazine derivative six times exceeds adaptogenic activity of ginseng and seven times that of amitriptyline. The rats in the control group were active for a bit longer time. Ginseng raised the time of activity by 17% at day 5. Caffeine essentially reduced work capacity and endurance. Amitriptyline showed adaptogenic activity at day 3 of the research (increase by 10.4%). Thiotriazolin also showed adaptogenic activity on day 3 of the research (increase by 30.17%). Thiocetam increased the time of activity by 78.55%. Substance 4 had adaptogenic activity too; it increased the time of activity in aversive conditions by 58.25%, which three times exceeds this parameter for ginseng and four times for amitriptyline.

Aim. In this research, we studied the parameters of blood biochemical analysis in rats with combined paracetamol-alcoholic liver injury after its pharmacological correction by newly synthesized partially hydrogenated pyridines (cyanothioacetamide derivatives).Materials and methods. 50 samples of new derivatives of partially hydrogenated pyridines synthesized on the basis of the “Chemex” Research Laboratory of the Vladimir Dal’ Lugansk National University underwent virtual bioscreening, which allowed the selection of 4 compounds, the biological activity of which may be associated with the effect on the protein synthesis and detoxifi cation function of the liver. The experiment was conducted on 48 white outbred male rats. For 14 days, the rats of the control and experimental groups were intragastrically injected with 1 ml of 40% ethanol and paracetamol at a dose of 500 mg/kg once a day. Pharmacocorrection with a thiotriazoline reference drug (50 mg/kg) and pyridine derivatives at a dose of 5 mg/kg was performed from the fourth day. On the 15th day, blood was sampled to determine the level of total bilirubin, alanine aminotransferase, aspartate aminotransferase and thymol turbidity test.Results. The value of total bilirubin in the blood of the rats treated with CV046 compounds was 34.88% lower than that in the control group. The animals of the test groups receiving CV047 also showed signifi cant differences with the control group in terms of bilirubin level (a decrease of 31.78%). The AST values in the blood of rats in the test groups had no signifi cant differences as compared with intact animals. Following 10 days of pharmacological correction of combined paracetamol-alcoholic liver injury with CV146, the total bilirubin level in the blood decreased by 26.36% in comparison with the control group, with the activity of ALT and AST demonstrating the levels of intact values.Conclusions. The conducted screening studies of four partially hydrogenated pyridines — cyanothioacetamide derivatives — using the model of combined paracetamol-alcoholic liver injury when used at a dose of 5 mg/kg during ten days have shown a high hepatoprotective and detoxifying activity of the following three compounds: СV046 (2-[(9-tert-butyl-1,5-dicyano4-oxo-3-azaspiro[5,5]undec-1-en-2-yl)thio]-N-(2-ethylphenyl)acetamide — IUPAC), СV047 (2-[(9-tert-butyl-1,5-dicyano-4-oxo-3-azaspiro[5,5]undec-1-en-2-yl)thio]-N-(4-fl uorophenyl) acetamide) and СV146 (benzyl 4-(4-chlorophenyl)-5-cyano-6-({2-[(3,4-dimethylphenyl)amino]-2-oxoethyl}thio)-2-methyl-1,4-dihydropyridine-3-carboxylate).

We conducted screening tests of 9 new organic compounds on a high-fat diet-induced obesity model with the use of palm oil.