Experimental Study of Dose-Dependent Endotheliotropic Effect of Atacl in Ischemic Brain Damage in Rats

Воронков, Андрей Владиславович; Oganesyan, É. T.; Pozdnyakov, D.I.; Абаев, Владимир Т.

doi:10.19163/1994-9480-2017-1(61)-54-58

Cited by 3 publications

(1 citation statement)

References 4 publications

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“…For instance, Pozdnyakov et al (2018) noted that under conditions of cerebral ischemia, the use of ATACL at a dosage of 100 mg/ kg contributed to the normalization of pro/antioxidant equilibrium by increasing the activity of superoxide dismutase, catalase and glutathione peroxidase, as well as by suppressing free radical lipid oxidation reactions, which can indicate a decrease in the concentration of diene adducts and TBA-active compounds, when using 4-hydroxy-3,5-di-tert-butyl cinnamic acid. In this case, the metabolic action of the ATACL compound can be aimed at stabilizing the mitochondrial function, which is realized through the normalization of the activity of mitochondrial subcomplexes V (F 1 F 0 ATP synthase) and IV (cytochrome c oxidase) (Voronkov et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Study of dose-dependent actoprotective effect of ATACL on physical performancend psychoemotional status of animals under exhausting exercise

Gerashchenko¹,

Поздняков²,

Voronkov³

2022

RRP

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Introduction: The aim of the study was to investigate the dose-dependent actoprotective effect of ATACL on physical performance and psychoemotional status of animals under conditions of exhausting exercise. Materials and methods: Outbred male mice (23–25 g) were used in the experiment. The test compound in various dosages, as well as the reference drug, were administered intragastrically 60 minutes before the forced swimming test for 10 days of the experiment. At the end of the physical activity, the psychoemotional status of the animals was assessed in the Open Field (OF) and Elevated plus maze (EPM) tests. Results and discussion: In the course of the experiment, it was found that under conditions of exhausting physical execise, a smooth increase in performance was observed in the group that had received the test compound 4-hydroxy-3,5-di-tert butyl cinnamic acid (ATACL) at a dosage of 100 mg/kg for 10 days. The peak of performance was recorded on the 8th day, which was 47.3% (p<0.05) higher than the physical activity of the mice treated with the reference drug ethylthiobenzimidazole hydrobromide (EBH). When assessing changes in the Open Field test, it was found that the test compound ATACL at a dosage of 100 mg/kg is also a leader in stabilizing the psychoemotional status of the animals, which is reflected in the improvement of the motor activity (the number of sectors crossed by 4.7 times (p< 0.05)), exploratory activity (an increase in the number of «peeps» and rearings by 8.5 times (p<0.05) and 12.7 times (p<0.05), respectively) and changes in the level of anxiety (a 2.5-time decrease in the number of short-term grooming acts (p<0.05)) in comparison with the negative control (NC) group. The results obtained in the EPM test are completely consistent with the results of the OF test; the most pronounced activity was observed for the ATACL compound at a dosage of 100 mg/kg. Conclusion: Based on the combination of reproducible methods, it can be concluded that the most pronounced actоprotective effect is exerted by the compound at a dosage of 100 mg/kg, not inferior, at the same time, to the reference drug EBН. Graphical abstract:

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Section: Discussionmentioning

confidence: 99%

Study of dose-dependent actoprotective effect of ATACL on physical performancend psychoemotional status of animals under exhausting exercise

Gerashchenko¹,

Поздняков²,

Voronkov³

2022

RRP

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Using Quantum-Chemical Parameters for Predicting Anti-Radical (Но∙) Activity of Related Structures Containing a Cinnamic Mold Fragment. I. Derivatives of Cinnamic Acid, Chalcon and Flavanon

Оганесян

Shatokhin

Глушко

2019

Farm. farmakol. (Pâtigorsk)

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45 compounds uniting 3 groups of derivatives of cinnamic acid, chalcone and flavanone, have been studied. Each of them includes 15 substances. The analyzed compounds contain a common structural fragment, which is a cinnamic acid residue (cinnamoyl fragment).The aimis to study the quantum-chemical parameters of the listed groups of the compounds in order to predict possible ways of their interaction with the most aggressive and dangerous of the active oxygen species (ROS) – a hydroxyl radical.Materials and methods.For the analyzed structures, the Mulliken charges (a.u.), bond numbers (Nμ), unsaturation index (IUA), and electron density values on all 9-carbon atoms of the cinnamoyl fragment have been determined. The calculations have been carried out on a workstation with an Intel Xeon E5-1620 3.5 GHz processor, 20 GB of RAM. The semi-empirical method PM7 was used (WinMopac 2016 program). The ORCA 4.1 program was used to calculate the energies of homolytic cleavage of the O – H bond.Results.The analysis of Mulliken charges (a.u.), bonded numbers (Nμ), unsaturation indices (IUA), and electron density revealed a number of regularities on the basis of which it can be concluded, that taking into account the nature of the substituent, the most probable for addition in the aryl residueare positions C-1, C-2, C-3, C-4 and C-5. In the propenone fragment, the radical НО∙ first attacks position 8, then 7. For the hydroxy-substituted, the energy of the homolytic breaking of the H – O bond has been determined and it has been established that the spatial difficulty of phenols (compounds 13k, 13x, 13f, 14k, 14x, 14f) H-O bonds are the smallest and on average are -160.63 kJ/mol. It has also been established that the higher the positive Mulliken charge on the carbon atom with which the phenolic hydroxyl is bound, the lower the energy of the homolytic breaking of the H – O bond and the more stable the resulting phenoxy radicalis.Conclusion.The carried out quantum chemical calculations allow us to conclude that the studied classes of compounds can be used to bind the hydroxyl radical formed in the body, causing various kinds of mutations, leading, among other things, to the development of oncological diseases.

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Using Quantum-Chemical Parameters for Predicting Anti-Radical (Но∙) Activity of Related Structures Containing a Cinnamoyl Fragment Ii. Derivatives of 2’,4’-Dihydroxychalcone, Flavanone and Flavone, Containing a Hydroxy Group in Position 7

Оганесян

Shatokhin

2020

Farm. farmakol. (Pâtigorsk)

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42 derivatives of 2’,4’-dihydroxychalcone, flavanone and flavone, containing the hydroxy group in position 7 (ring "A"), as well as substituents in the ring "B", have been studied.The aim is to study the quantum-chemical parameters of 2',4'-dihydroxychalcone, flavanone and flavone derivatives containing a hydroxy group in position 7, in order to identify the effect of substituents on Mulliken charges (a.e) in the aromatic core "A", bond numbers (Nµ), the unsaturation index (IUA) and the electron density of the carbon atoms of the cinnamoyl fragment.Materials and methods. The listed above parameters have been calculated by the semi-empirical method PM7 (WinMopac 2016 program) on the workstation with an Intel Xeon E5-1620 3.5 GHz processor, 20 GB of RAM.Results. The analysis of the values of quantum-chemical parameters, as well as their comparison with the corresponding indicators presented in Report I, revealed a number of important features associated with the influence of the hydroxy group in position 7 (ring "A") on the studied quantum-chemical parameters of molecules. It has been established that the hydroxy group in the ring “A” does not significantly affect the Mulliken charge and the electron density of the carbon atoms of the propenone unit C-7→C-8→C-9. On atom C-9 (carbonyl carbon), the Mulliken charge always has a positive value, and the electron density is about 3.4670-3.4840 for all three groups of compounds. The transition from 2’,4’-dihydroxychalcone to flavanone and flavone by the formation of the pyrone heterocycle, is accompanied by an increase in the negative charge on C-8, which can be explained by the involvement of the oxygen heteroatom in the transmission of electronic effects. The hydroxy group in the ring “A”, has practically no effect on the charge and electron density of atoms. An analysis of the values of bond numbers and unsaturation indices suggests that atoms C-1 of 2’,4’-dihydroxychalcone and 7-hydroxyflavanone derivatives, are characterized by the lowest Nµ value; the lowest bond numbers are characteristic for atom C-8 derivatives of 7-hydroxyflavone. Consequently, the primary attack of the HO·radical will be directed at C-1 (in chalcones and flavanones) and at C-8 in flavones.Conclusion. The performed quantum-chemical calculations make it possible to analyze the effect on the main quantum-chemical parameters of the molecule, which can be useful in predicting the biological activity of flavanoid compounds due to their antiradical effect on reactive oxygen intermediate species (ROIs).

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Experimental Study of Dose-Dependent Endotheliotropic Effect of Atacl in Ischemic Brain Damage in Rats

Cited by 3 publications

References 4 publications

Study of dose-dependent actoprotective effect of ATACL on physical performancend psychoemotional status of animals under exhausting exercise

Study of dose-dependent actoprotective effect of ATACL on physical performancend psychoemotional status of animals under exhausting exercise

Using Quantum-Chemical Parameters for Predicting Anti-Radical (Но∙) Activity of Related Structures Containing a Cinnamic Mold Fragment. I. Derivatives of Cinnamic Acid, Chalcon and Flavanon

Using Quantum-Chemical Parameters for Predicting Anti-Radical (Но∙) Activity of Related Structures Containing a Cinnamoyl Fragment Ii. Derivatives of 2’,4’-Dihydroxychalcone, Flavanone and Flavone, Containing a Hydroxy Group in Position 7

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