New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents
Introduction: To solve the problem of complex and safe pharmacological correction of metabolic disorders, including hyperlipidemia, hyperglycemia, and liver lesions is currently very important. With this in mind, the new derivatives of cyanothioacetamide with a dihydropyridine framework, with a pote...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Belgorod National Research University
2024-09-01
|
| Series: | Research Results in Pharmacology |
| Subjects: | |
| Online Access: | https://rrpharmacology.ru/index.php/journal/article/view/483 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841554657581727744 |
|---|---|
| author | Elena S. Ketova Anna V. Myazina Elena Yu. Bibik Sergey G. Krivokolysko |
| author_facet | Elena S. Ketova Anna V. Myazina Elena Yu. Bibik Sergey G. Krivokolysko |
| author_sort | Elena S. Ketova |
| collection | DOAJ |
| description | Introduction: To solve the problem of complex and safe pharmacological correction of metabolic disorders, including hyperlipidemia, hyperglycemia, and liver lesions is currently very important. With this in mind, the new derivatives of cyanothioacetamide with a dihydropyridine framework, with a potential effect on lipid and carbohydrate metabolism and the functioning of the liver are of great interest.
Materials and Methods: To conduct an experiment, three samples were selected from an extensive library of new cyanothioacetamide derivatives, which, according to in silico studies, proved promising towards the positive effect on lipid and carbohydrate metabolism, as well as towards the protective effect on the liver. To study the compounds in vivo, metabolic disorders were simulated in Wistar rats by long -term alimentary and subsequent dexamethasone loads. The pharmacological efficacy of new compounds AZ-383, AZ-257, AZ-020 (administered in a dose of 1 mg/kg for 14 days) was assessed in comparison with metformin (300 mg/kg for 14 days) and vildagliptin (8 mg/kg for 14 days) by determining the biochemical indicators of blood (ALT, AST, total bilirubin, total cholesterol, triglycerides, and glucose), morphological and morphometric studies of the liver sections, and the study of immunohistochemical indicators of hepatocyte proliferation. The experimental results were statistically processed using the recognized methods of mathematical statistics. When processing the experimental data, the average arithmetic (AA) was determined. The statistical significance of the compared options was determined on the basis of the Student’s t-test, with the critical value of the Student’s t-test equal to 2.101 and the significance level α = 0.05.
Results: The study shows that all the new compounds studied in the experiment – AZ-383, AZ-257, AZ-020 – have hypolipidemic and hepatoprotective properties, which manifested in the reduced levels of liver biochemical markers of blood, which had increased after simulating metabolic disorders, in the reduced concentration of total cholesterol and triglycerides in blood, in the normalization of liver microarchitecture, as well as in the proliferative activity of hepatocytes.
Discussion: The hepatoprotective and hypolypidemic properties of the new derivatives of cyanothioacetamide with a dihydropyridine framework, which were determined while conducting the experiment, can be accounted for by their effects on the biotargets, identified for AZ-383, AZ-257, and AZ-020 in silico. According to the results, the most pronounced hepatoprotective activity was found in AZ-383 (intragastrically, 1 mg/kg for 14 days). The Ki-67 proliferation index under the influence of this compound was registered at the level of 1.48±0.03%, which exceeds this indicator in the control animals and proves a significant hepatoprotective activity of AZ-383.
Conclusion: The results show good prospects and high efficacy of the new studied cyanothioacetamide derivatives, such as AZ-383, AZ-257, AZ-020 (in a dose of 1 mg/kg), in terms of comprehensive correction of metabolic disorders. Further study is needed for this class of compounds. |
| format | Article |
| id | doaj-art-b9b63dd2486b4c30a229d0cee7eb0bfe |
| institution | Kabale University |
| issn | 2658-381X |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj-art-b9b63dd2486b4c30a229d0cee7eb0bfe2025-01-08T12:32:23ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2024-09-01103617110.18413/rrpharmacology.10.483New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agentsElena S. Ketova0https://orcid.org/0000-0002-4595-8103Anna V. Myazina1https://orcid.org/0000-0001-5736-2385Elena Yu. Bibik2https://orcid.org/0000-0001-7470-608XSergey G. Krivokolysko3https://orcid.org/0000-0001-9879-9217BestDoctor Ltd.V.I. Vernadsky Crimean Federal UniversitySaint Luka Lugansk State Medical UniversityVladimir Dahl Lugansk State UniversityIntroduction: To solve the problem of complex and safe pharmacological correction of metabolic disorders, including hyperlipidemia, hyperglycemia, and liver lesions is currently very important. With this in mind, the new derivatives of cyanothioacetamide with a dihydropyridine framework, with a potential effect on lipid and carbohydrate metabolism and the functioning of the liver are of great interest. Materials and Methods: To conduct an experiment, three samples were selected from an extensive library of new cyanothioacetamide derivatives, which, according to in silico studies, proved promising towards the positive effect on lipid and carbohydrate metabolism, as well as towards the protective effect on the liver. To study the compounds in vivo, metabolic disorders were simulated in Wistar rats by long -term alimentary and subsequent dexamethasone loads. The pharmacological efficacy of new compounds AZ-383, AZ-257, AZ-020 (administered in a dose of 1 mg/kg for 14 days) was assessed in comparison with metformin (300 mg/kg for 14 days) and vildagliptin (8 mg/kg for 14 days) by determining the biochemical indicators of blood (ALT, AST, total bilirubin, total cholesterol, triglycerides, and glucose), morphological and morphometric studies of the liver sections, and the study of immunohistochemical indicators of hepatocyte proliferation. The experimental results were statistically processed using the recognized methods of mathematical statistics. When processing the experimental data, the average arithmetic (AA) was determined. The statistical significance of the compared options was determined on the basis of the Student’s t-test, with the critical value of the Student’s t-test equal to 2.101 and the significance level α = 0.05. Results: The study shows that all the new compounds studied in the experiment – AZ-383, AZ-257, AZ-020 – have hypolipidemic and hepatoprotective properties, which manifested in the reduced levels of liver biochemical markers of blood, which had increased after simulating metabolic disorders, in the reduced concentration of total cholesterol and triglycerides in blood, in the normalization of liver microarchitecture, as well as in the proliferative activity of hepatocytes. Discussion: The hepatoprotective and hypolypidemic properties of the new derivatives of cyanothioacetamide with a dihydropyridine framework, which were determined while conducting the experiment, can be accounted for by their effects on the biotargets, identified for AZ-383, AZ-257, and AZ-020 in silico. According to the results, the most pronounced hepatoprotective activity was found in AZ-383 (intragastrically, 1 mg/kg for 14 days). The Ki-67 proliferation index under the influence of this compound was registered at the level of 1.48±0.03%, which exceeds this indicator in the control animals and proves a significant hepatoprotective activity of AZ-383. Conclusion: The results show good prospects and high efficacy of the new studied cyanothioacetamide derivatives, such as AZ-383, AZ-257, AZ-020 (in a dose of 1 mg/kg), in terms of comprehensive correction of metabolic disorders. Further study is needed for this class of compounds.https://rrpharmacology.ru/index.php/journal/article/view/483new cyanothioacetamide derivatives with a dihydropyridine frameworkmetabolic disordershyperlipidemiahepatoprotective activitypharmacological correction |
| spellingShingle | Elena S. Ketova Anna V. Myazina Elena Yu. Bibik Sergey G. Krivokolysko New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents Research Results in Pharmacology new cyanothioacetamide derivatives with a dihydropyridine framework metabolic disorders hyperlipidemia hepatoprotective activity pharmacological correction |
| title | New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents |
| title_full | New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents |
| title_fullStr | New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents |
| title_full_unstemmed | New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents |
| title_short | New compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents |
| title_sort | new compounds with a dihydropyridine framework as promising hypolipidemic and hepatoprotective agents |
| topic | new cyanothioacetamide derivatives with a dihydropyridine framework metabolic disorders hyperlipidemia hepatoprotective activity pharmacological correction |
| url | https://rrpharmacology.ru/index.php/journal/article/view/483 |
| work_keys_str_mv | AT elenasketova newcompoundswithadihydropyridineframeworkaspromisinghypolipidemicandhepatoprotectiveagents AT annavmyazina newcompoundswithadihydropyridineframeworkaspromisinghypolipidemicandhepatoprotectiveagents AT elenayubibik newcompoundswithadihydropyridineframeworkaspromisinghypolipidemicandhepatoprotectiveagents AT sergeygkrivokolysko newcompoundswithadihydropyridineframeworkaspromisinghypolipidemicandhepatoprotectiveagents |