Some aspects of cerebroprotective activity of 4-hydro xy-3,5-di-tretboutyle of cinnamic acid in ischemic damage of the brain in experiment

Voronkov, Andrey; Абаев, Владимир Т.; Оганесян, Эдуард Тоникович; Pozdnyakov, D.I.

doi:10.14300/mnnc.2018.13025

Cited by 7 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In previous studies, the cerebroprotective properties of 4hydroxy-3,5-di-tertbutyl cinnamic acid were established (13), but the detailed mechanism of action of this compound was not established. This study represent data on the positive effect of 4-hydroxy-3,5-di-tertbutyl cinnamic acid on bioenergetic processes occurring in the brain mitochondria under cerebral ischemia, and large laboratory animals that are more susceptible to ischemic effects were used as a biological model.…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, it can be assumed that a targeted effect on mitochondria can reduce the degree of brain damage in conditions of ischemic stroke. In previous studies, potential cerebroprotective properties of 4hydroxy-3,5-di-tertbutyl cinnamic acid have been identified, which may also be associated with the restoration of mitochondrial function by stabilizing the activity of cytochrome C oxidase and ATP synthetase (mitochondrial complex IV and V respectively) (13). In this respect, the aim of this study was to evaluate the effect of 4-hydroxy-3,5-di-tertbutyl cinnamic acid on the change of functional activity of the brain mitochondria of rabbits in conditions of cerebral ischemia.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Administration of 4-Hydroxy-3,5-Di-Tertbutyl Cinnamic Acid Restores Mitochondrial Function in Rabbits with Cerebral Ischemia

Pozdnyakov

Hadzhieva

Pozdnyakova

2022

Serbian Journal of Experimental and Clinical Research

View full text Add to dashboard Cite

The aim of the study is to evaluate the effect of 4-hydroxy-3,5- di-tertbutyl cinnamic acid on the change in mitochondrial function under conditions of experimental cerebral ischemia in rabbits. The study was performed on 48 male rabbits, which were used for modeling permanent cerebral ischemia by occlusion of the common carotid arteries. The test compound was administered before modeling ischemia for 14 days and after the occurrence of reproducing ischemia, in a similar time interval. After that, neurological deficit and the parameters of mitochondrial respiration, the intensity of anaerobic processes, the latent opening time of the mitochondrial permeability transition pore, the value of the mitochondrial membrane potential and the concentration of caspase – 3 were determined. The administration of 100 mg/kg of 4-hydroxy-3,5-di-tertbutyl cinnamic acid into the animals reduced neurological deficit and restored the mitochondrial membrane potential. Prophylactic administration of 4-hydroxy- 3,5-di-tertbutyl cinnamic acid, contributed to an increase in ATPgenerating ability, the maximum level of respiration and respiratory capacity by 4.1 times (p<0.01), 4.8 times (p<0.01) and 4.3 times (p<0.01), respectively. With therapeutic administration, these indicators increased by 11 times (p<0.01), 12.2 times (p<0.01) and 8.6 times (p<0.01), respectively. Also, both the prophylactic and therapeutic use of 4-hydroxy-3,5-di-tret-butyl cinnamic acid normalized aerobic/anaerobic metabolism, as well as reduced the concentration of caspase-3. Based on the obtained data, significant cerebroprotective properties of 4-hydroxy-3,5- di-tertbutyl cinnamic acid can be assumed. Moreover, the potential mechanism of action of this compound may be mediated by the normalization of mitochondrial function.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Administration of 4-Hydroxy-3,5-Di-Tertbutyl Cinnamic Acid Restores Mitochondrial Function in Rabbits with Cerebral Ischemia

Pozdnyakov

Hadzhieva

Pozdnyakova

2022

Serbian Journal of Experimental and Clinical Research

View full text Add to dashboard Cite

show abstract

“…Ранее нами, в соответствии с прогнозом, было получено производное коричной кислоты, которое в арильном остатке главной цепи сопряжения (кольцо «В») содержало трет-бутильные радикалы в положениях С-2 и С-4 и гидроксигруппу у С-3 [12]. Оно проявило высокую церебропротекторную, антиоксидантную, эндотелиопротекторную и актопротекторную активности [15][16][17][18]:…”

Section: электронная плотностьunclassified

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)

View full text Add to dashboard Cite

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).

show abstract

“…Следует отметить, что соединение 14к (4-гидрокси-3,5-ди-трет-бутилкоричная кислота) ранее нами было синтезировано в соответствии с прогнозом [11], поскольку для этого вещества прогнозировалась высокая активность. Экспериментальное изучение фармакологических свойств подтвердило наш прогноз: вещество характеризуется церебропротекторной [17], антиоксидантной [18], эндотелиопротекторной [19] и актопротекторной [20] активностью.…”

Section: рисунок 2 динамика изменения потенциальной энергии в процесunclassified

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)

View full text Add to dashboard Cite

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.

show abstract

Some aspects of cerebroprotective activity of 4-hydro xy-3,5-di-tretboutyle of cinnamic acid in ischemic damage of the brain in experiment

Cited by 7 publications

References 0 publications

Administration of 4-Hydroxy-3,5-Di-Tertbutyl Cinnamic Acid Restores Mitochondrial Function in Rabbits with Cerebral Ischemia

Administration of 4-Hydroxy-3,5-Di-Tertbutyl Cinnamic Acid Restores Mitochondrial Function in Rabbits with Cerebral Ischemia

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

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

Contact Info

Product

Resources

About