In vivo evaluation of the anti-inflammatory properties of the original derivatives of α-cyanothioacetamide
- Authors: Gusev D.F.1, Bibik E.Y.2, Oleynik I.S.1, Krivokolisko S.G.3,4, Ameline N.D.5, Bukhtoyarova D.R.1
-
Affiliations:
- St. Luke's State Medical University
- Lugansk State Medical University named after St. Luke
- NIL "HimEks"
- Lugansk State University named after Vladimir Dahl
- Lugansk Republican Clinical Hospital
- Issue: Vol 13 (2024): Материалы XX Международного Бурденковского научного конгресса 18-20 апреля 2024 года
- Pages: 213-215
- Section: Клиническая фармакология и фармакоэкономика
- URL: https://new.vestnik-surgery.com/index.php/2415-7805/article/view/9241
Cite item
Full Text
Abstract
The work raises the question of the synthesis of new drugs that have analgesic and anti-inflammatory activity, high efficiency and safety in their use. The article examines the anti-inflammatory activity of new α-cyanothioacetamide derivatives in the classical pharmacological test of dextran paw edema. The purpose of the study is to evaluate the anti-inflammatory properties of the original α-cyanothioacetamide derivatives in in vivo experiments. New derivatives of α-cyanothioacetamide with laboratory codes d02-128 and d02-122 are the leading samples in the test; their effectiveness is 1.57-10.8 times higher than nimesulide.
Full Text
Relevance. The relevance of the study is due to the need to search for new effective and safe anti-inflammatory drugs, which in their pharmacological activity exceed existing NSAIDs on the pharmaceutical market, and do not have the typical undesirable effects of the NSAID group (gastrotoxicity, nephrotoxicity, cardiotoxicity, hematotoxicity and others). New α-cyanothioacetamide derivatives, synthesized by us on the basis of the ChemEx Research Laboratory, have already shown high antinociceptive activity in studies [1, 2, 4]. A virtual bioscreening was carried out to determine the possible biotargets of each of the new samples [3]. These results suggest the presence of anti-inflammatory activity of α-cyanothioacetamide derivatives.
The purpose of the work was to evaluate the anti-inflammatory properties of the original α-cyanothioacetamide derivatives in in vivo experiments.
Materials and methods of research. The experiment was carried out on experimental male rats in the amount of 140 individuals. Laboratory animals were divided into 14 groups of 10 animals in each cage (average weight 190-240 g). The experiments were performed in accordance with the methodological recommendations for preclinical study of drugs. The effectiveness of the samples was studied using the acute dextran paw edema test in rats. The latter was caused by subcutaneous injection of 0.1 ml of 6% dextran solution into the right hind paw of a laboratory rat. The studied new synthesized derivatives of α-cyanothioacetamide were administered intragastrically at a dose of 5 mg per 1 kg of animal weight 1.5 hours before induction of edema. The comparison drugs were: acetylsalicylic acid 50 mg/kg, indomethacin 7 mg/kg, acetaminophen 50 mg/kg, nimesulide 5 mg/kg. The volume of the induced paws was measured after 1 and 3 hours of simulated edema.
Research results. As a result of subplantar injection of a 6% dextran solution, an inflammatory reaction is observed, which is characterized by severe swelling, hyperemia, pain and dysfunction of the injected paw. In rats of the intact group, which were administered an intragastric solution of 0.9% NaCl, no difference in the girth of the paw and left paws was found, since edema was not induced. In the control group (without pharmacocorrection), the administration of dextran led to an increase in the volume of the paw by 47% compared to the symmetrical limb. The new α-cyanothioacetamide derivatives under investigation with laboratory codes d02-139, d02-149, d02-168, d02-123, d02-122, d02-128, d02-133 and d02-141 have anti-inflammatory activity to varying degrees. The leading examples in this vein are the heterocyclic compounds d02-123 and d02-128. When administered through a gastric tube, sample d02-123, the difference in the girth of the paws is 21.96%, and the heterocyclic compound with code d02-128 is 21.75%. In comparison with nimesulide (the difference in paw circumference is 30.98%), these samples are 1.42 times more effective, respectively. 3 hours after the injection of dextran solution under the plantar aponeurosis, a rapid increase in the anti-exudative activity of sample d02-123 is observed (the difference in the girth of the paws is 1.96%). The decongestant effectiveness is 10.8 times higher than that of nimesulide. At the 3-hour mark, sample d02-128 is 1.57 times more effective than nimesulide.
Conclusion. Thus, we have identified the anti-inflammatory properties of new α-cyanothioacetamide derivatives with codes d02-139, d02-149, d02-168, d02-123, d02-122, d02-128, d02-133 and d02-141, using the classic dextran test swelling of the paw. The leading samples are d02-123 and d02-128, which are 1.57-10.8 times more effective than nimesulide. To further study anti-inflammatory drugs, it is necessary to conduct a series of pharmacological tests and analyze the data obtained using statistical processing.
About the authors
Daniil Fyodorovich Gusev
St. Luke's State Medical University
Email: irina.oleynik.0511@gmail.com
ORCID iD: 0009-0003-8983-2267
4th year student, Faculty of Medicine
Russian Federation, 291045, Russia, Lugansk People's Republic, Lugansk, 50th Anniversary of the Defense of Lugansk, 1g.Elena Yuryevna Bibik
Lugansk State Medical University named after St. Luke
Email: helen_bibik@mail.ru
ORCID iD: 0000-0001-7470-608X
Doctor of Medical Sciences, Professor, Head of the Department of Fundamental and Clinical Pharmacology
Russian Federation, 291045, Russia, Lugansk People's Republic, Lugansk, 50th Anniversary of the Defense of Lugansk, 1g.Irina Sergeevna Oleynik
St. Luke's State Medical University
Author for correspondence.
Email: farm.irina.oleynik1999@gmail.com
ORCID iD: 0009-0009-5386-181X
Assistant of the Department of Fundamental and Clinical Pharmacology
Russian Federation, 291045, Russia, Lugansk People's Republic, Lugansk, 50th Anniversary of the Defense of Lugansk, 1g.Sergey Gennadievich Krivokolisko
NIL "HimEks"; Lugansk State University named after Vladimir Dahl
Email: ksg-group-lugansk@mail.ru
ORCID iD: 0000-0001-9879-9217
Doctor of Chemical Sciences, Professor
Russian Federation, 291034, Russia, Lugansk People's Republic, Lugansk, kv. Molodezhny, 20a.Nikita Dmitrievich Ameline
Lugansk Republican Clinical Hospital
Email: nikita.ly82@mail.ru
ORCID iD: 0000-0001-8751-8969
He has been a resident for 2 years, specializing in Gastroenterology
Russian Federation, 291045, Russia, Lugansk People's Republic, Lugansk, ul. 50 years of Defense of Lugansk, 14Daria Romanovna Bukhtoyarova
St. Luke's State Medical University
Email: darya.rupengey.00@mail.ru
ORCID iD: 0009-0001-6658-3574
6th year student, Faculty of Medicine
Russian Federation, 291045, Russia, Lugansk People's Republic, Lugansk, 50th Anniversary of the Defense of Lugansk, 1g.References
- Бибик, Е.Ю. Новые производные цианотиоацетамида как потенциальные болеутоляющие средства / Е.Ю. Бибик, И.С. Олейник, К.А. Фролов, В.В. Доценко, С.Г. Кривоколыско // Журнал Фармацевтическое дело и технология лекарств.– 2022. – №4. – С. 15-16. doi: 10.33920/med-13-2208-02.
- Бочева, А. А. Исследование болеутоляющей активности новых частично гидрированных пиридинов, производных α-цианотиоацетамида в фармакологическом тесте тепловой иммерсии хвоста на белых крысах / А. А. Бочева, Е. Ю. Бибик, С. Г. Кривоколыско // Научно-медицинский вестник Центрального Черноземья. – 2023. – № 93. – С. 37-43.
- Олейник, И.С. Предварительный скрининг потенциальных анальгетических средств среди производных цианотиоацетамида / И.С. Олейник, Е.Ю. Бибик, А. С. Саул [и др.]. // Журнал: ГЛАВВРАЧ. – 2022. –– №8. – С. 30-31.
- Bibik, I.V. Empirical determination of the degree of analgesic activity of some new 3-aminothieno[2,3-b]pyridines and 1,4-dihydropyridines based on a complex criterion / I.V. Bibik, E. Yu. Bibik, K. A. Frolov et al. // Research Results in Pharmacology. — 2023. — №9(2). — Р. 67-74.
Supplementary files
There are no supplementary files to display.
