EXPERIMENTAL RESEARCH
Pharmacology
doi: 10.25005/2074-0581-2026-28-2-480-490
RELATIONSHIP BETWEEN THE IN SILICO AND IN VIVO ANTIDIABETIC AND ANTIATHEROSCLEROTIC PROPERTIES OF NOVEL DIHYDROPYRIDINE AND THIENOPYRIDINE DERIVATIVES

E.YU. BIBIK1, E.S. KETOVA2, S.G. KRIVOKOLYSKO1,3

1St. Luke Lugansk State Medical University, Lugansk, Russian Federation
2Department of Endocrinology, LLC «Rays of Health», Moscow, Russian Federation
3Vladimir Dahl Lugansk State University, Lugansk, Russian Federation

Objective: To evaluate the relationship between the in silico and in vivo antidiabetic and antiatherosclerotic properties of novel dihydropyridine and thienopyridine derivatives using an experimental model of combined dietary loading followed by dexamethasone administration.

Methods: Substances synthesized at the Research Laboratory “ChemEx” of Vladimir Dahl Lugansk State University were subjected to virtual bioscreening, which made it possible to identify several lead compounds: AZ-383, AZ-023, TD-0331, and mar-014. The experiment was performed on 56 mature male Wistar rats. The control group consisted of rats in which metabolic disorders were modeled by dietary and dexamethasone loading. In four experimental groups, after modeling the disorders, the novel compounds were administered intragastrically for 14 days at a dose of 1.5 mg/kg: AZ-383 in experimental group No. 1, AZ-023 in experimental group No. 2, TD-0331 in experimental group No. 3, and mar-014 in experimental group No. 4. Animals in the comparison groups received metformin, atorvastatin, and imunofan. When the animals were removed from the experiment, blood glucose, total cholesterol, and triglyceride levels were determined.

Results: High-fat and high-carbohydrate loading, followed by dexamethasone administration, led to the development of carbohydrate and lipid metabolic disorders, with blood glucose 9.8±0.9 mmol/L, total cholesterol 3.0±0.4 mmol/L, and triglycerides 2.4±0.7 mmol/L. In all experimental groups treated with the novel compounds, blood glucose, total cholesterol, and triglyceride levels did not differ statistically from the corresponding parameters in the intact group of animals.

Conclusion: The novel cyanothioacetamide derivatives studied in the experiment, designated AZ-383, AZ-023, TD-0331, and mar-014, exhibit antidiabetic and antiatherosclerotic activity, as evidenced by reductions in glycemia and total blood cholesterol and triglyceride concentrations in a model of metabolic disorders induced by combined dietary loading followed by dexamethasone administration.

Keywords: Dihydropyridine, thienopyridine, cyanothioacetamide, novel derivatives, antidiabetic properties, antiatherosclerotic activity, combined dietary loading, dexamethasone loading.

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Authors' information:

Bibik Elena Yurievna,
Doctor of Medical Sciences, Full Professor, Head of the Department of Fundamental and Clinical Pharmacology, St. Luke Lugansk State Medical University
ORCID ID: 0000-0002-2622-186X
E-mail: helen_bibik@mail.ru

Ketova Elena Sergeevna, Candidate of Medical Sciences, Endocrinologist, LLC «Rays of Health»
ORCID ID: 0000-0002-4595-8103
E-mail: ketova_elena@mail.ru

Krivokolysko Sergey Gennadievich, Doctor of Chemical Sciences, Head of the Research Laboratory "СhemEx", Head of the Department of Chemistry and Innovative Chemical Technologies, Vladimir Dahl Lugansk State University; Principal Researcher of Research Laboratory, St. Luke Lugansk State Medical University
ORCID ID: 0000-0001-9879-9217
Е-mail: ksg-group-lugansk@mail.ru

Information about support in the form of grants, equipment, medications

The work was carried out with the financial support of research conducted within the framework of the state assignment of the Ministry of Science and Higher Education of Russia on the topic “Novel heterocyclic derivatives of methylene-active nitriles, thioamides, and selenamides: Synthesis, properties, and biological activity” (code “FREE-2023-0002”), as well as with the financial support of research conducted within the framework of the state assignment of the Ministry of Health of Russia on the topic “Search for new highly effective and safe medicinal agents among previously unknown domestically produced heterocyclic cyanothioacetamide derivatives” (code “ZUNP-2024-0002”). The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Ketova Elena Sergeevna
Candidate of Medical Sciences, Endocrinologist, LLC «Rays of Health»

127015, Russian Federation, Moscow, Vyatskaya str., 27, building 15

Tel.: +7 (905) 6571280

E-mail: ketova_elena@mail.ru


This work is licensed under a Creative Commons Attribution 4.0 International License.

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