Pathophysiology
doi: 10.25005/2074-0581-2023-25-4-499-508
EVALUATION OF HEMATOTOXICITY OF NEW DERIVATIVES OF CONDENSED 3-AMINOTHIENO[2,3-b]PYRIDINES AND 1,4-DIHYDROPYRIDINES WITH HIGH ANALGESIC ACTIVITY

I.V. BIBIK1, A.A. PANKOV2, K.A. FROLOV2, V.V. DOTSENKO3,4, S.G. KRIVOKOLYSKO1,2, E.YU. BIBIK1

1Lugansk State Medical University named after St. Luke, Lugansk, Russian Federation
2Lugansk State University named after Vladimir Dal, Lugansk, Russian Federation
3Kuban State University, Krasnodar, Russian Federation
4North Caucasus Federal University, Stavropol, Russian Federation

Objective: To assess changes in blood parameters in rats after a two-week administration of the most commonly used clinically NSAIDs and new derivatives of the 3-aminothieno[2,3-b]pyridine and 1,4-dihydronicotinamide series with the most pronounced analgesic activity.

Methods: Ten low molecular weight ligands were chosen after screening various ligands. These ligands are capable of interacting with receptors and enzymes that are involved in the antinociceptive system. They contain fragments of 3-aminothieno[2,3-b]pyridine and 1,4-dihydronicotinamide. Samples with laboratory codes AZ023, AZ169, AZ213, AZ257, AZ729, AZ383, AZ331, AZ420, AU04271, AU04288 were selected for the experiment. Among them, AZ383, AZ331, AZ023, and AZ420 were chosen. The study involved 36 white male rats weighing between 250-280 g. Blood was collected via the femoral vein and analyzed using standard methods for erythrocyte, leukocyte, platelet, hemoglobin, and erythrocyte sedimentation rate (ESR) levels.

Results: According to experimental studies, unlike the reference drug, the compounds studied do not cause leukopenia. In addition, only a tendency to decrease the number of platelets was detected for compounds AZ023, AZ331, and AZ383 with pronounced analgesic and anti-inflammatory activity, which requires additional research.

Conclusion: Studies conducted on the safety of using derivatives of condensed 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridines have shown promising results for further preclinical development. These derivatives can become highly effective and safe agents for alleviating pain and inflammation of various origins and severity in the future.

Keywords: Blood test, hematotoxicity, pain syndrome, analgesic activity, thienopyridines, 1,4-dihydropyridines.

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Authors' information:

Bibik Igor Valerievich,
Candidate of Medical Sciences, Associate Professor of the Department of Surgical Dentistry, Lugansk State Medical University named after St. Luke
ORСID ID: 0000-0003-4053-1431
E-mail: dr.bibik.i.v@yandex.ru.

Pankov Andrey Aleksandrovich,
Doctor of Technical Sciences, Professor of the Department of Transport Technologies, Lugansk State University named after Vladimir Dal
ORCID ID: 0000-0003-2813-8231
E-mail: app.post@rambler.ru

Frolov Konstantin Aleksandrovich,
Candidate of Chemical Sciences, Associate Professor of the Department of Pharmaceutical Chemistry and Pharmacognosy, Lugansk State Medical University named after St. Luke; Chief Engineer of the Research Laboratory "СhemEx", Lugansk State University named after Vladimir Dal
ORCID ID: 0000-0002-8045-7582
E-mail: ka.frolov@inbox.ru

Dotsenko Viktor Viktorovich,
Doctor of Chemical Sciences, Head of Department of Organic Chemistry and Technologies, Kuban State University; Senior Researcher of the Research Laboratory "СhemEx", Lugansk State University named after Vladimir Dal; Senior Researcher of the Department of Organic Chemistry, North Caucasus Federal University
ORCID ID: 0000-0001-7163-0497
E-mail: victor_dotsenko_@mail.ru

Krivokolysko Sergey Gennadievich,
Doctor of Chemical Sciences, Head of the Department of Pharmaceutical Chemistry and Pharmacognosy, Lugansk State Medical University named after St. Luke; Head of the Research Laboratory "СhemEx", Lugansk State University named after Vladimir Dal
ORCID ID: 0000-0001-9879-9217
E-mail: ksg-group-lugansk@mail.ru

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

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

The authors did not receive financial support from manufacturers of medicines and medical equipment

Conflicts of interest: No conflict

Address for correspondence:

Bibik Elena Yurievna
Doctor of Medical Sciences, Head of the Department of Fundamental and Clinical Pharmacology, Lugansk State Medical University named after St. Luke

291045, Russian Federation, Lugansk, sq. 50th Anniversary of the Defense of Lugansk, 1g

Tel.: +7 (8572) 022347113

E-mail: helen_bibik@mail.ru

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