pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2020-8-2-78-85pmedpharm-685Research ArticleФАРМАКОЛОГИЯ И КЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯPHARMACOLOGY AND CLINICAL PHARMACOLOGYАНТИТРОМБОТИЧЕСКАЯ АКТИВНОСТЬ НОВОГО ПРОИЗВОДНОГО БЕНЗИМИДАЗОЛА, ИМЕЮЩЕГО В СВОЕЙ СТРУКТУРЕ ПРОСТРАНСТВЕННО ЗАТРУДНЕННЫЙ ФЕНОЛЬНЫЙ ЗАМЕСТИТЕЛЬANTITROMBOTIC ACTIVITY OF A NEW BENZIMIDAZOLE DERIVATIVE WITH A SPATIALLY DIFFICULT PHENOLIC SUBSTITUTE IN ITS STRUCTUREhttps://orcid.org/0000-0002-7185-4826СпасовАлександр АлексеевичSpasovAlexander A.

академик РАН, доктор медицинских наук, профессор, заведующий кафедрой фармакологии и биоинформатики

aspasov@mail.ruhttps://orcid.org/0000-0003-1406-6919КучерявенкоАида ФатиховнаKucheryavenkoAida F.

доктор медицинских наук, доцент, профессор кафедры фармакологии и биоинформатики

aidakuchryavenko@yandex.ruhttps://orcid.org/0000-0003-4376-6332ГайдуковаКсения АндреевнаGaidukovaKsenia A.

ассистент кафедры фармакологии и биоинформатики

ksenijagajjdukva@rambler.ruhttps://orcid.org/0000-0001-8340-1296ЧерниковМаксим ВалентиновичChernikovMaxim V.

доктор медицинских наук, заведующий кафедрой биологии ифизиологии

Doctor of Sciences (Medicine), the Head of the Department of Biology and Physiology

pharmax@list.ruhttps://orcid.org/0000-0003-0865-6656ЖуковскаяОльга НиколаевнаZhukovskayaOlga N.

кандидат химических наук, научный сотрудник лаборатории органического синтеза

zhukowskaia.ol@yandex.ruВолгоградский государственный медицинский университетРоссияVolgograd State Medical UniversityRussian FederationПятигорский медико-фармацевтический институт - филиал ВолгГМУРоссияPyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical UniversityRussian FederationНИИ физической и органической химии Южного федерального университетаРоссияResearch Institute of Physical and Organic Chemistry, Southern Federal UniversityRussian Federation202014102020827885Copyright © Спасов А.А., Кучерявенко А.Ф., Гайдукова К.А., Черников М.В., Жуковская О.Н., 20202020Спасов А.А., Кучерявенко А.Ф., Гайдукова К.А., Черников М.В., Жуковская О.Н.Spasov A.A., Kucheryavenko A.F., Gaidukova K.A., Chernikov M.V., Zhukovskaya O.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/685

Цель – изучение антитромбогенных свойств соединения РУ-1144 с ранее выявленной выраженной антиагрегантной и антиоксидантной активностью, на модели артериального тромбоза сонной артерии крыс, индуцированного хлоридом железа (III), в сравнении с известными антиагрегантными препаратами – ацетилсалициловой кислотой и клопи-догрелом, а также антиоксидантным препаратом – этилметилгидроксипиридина сукцинат.Материалы и методы. Антитромботическая активность соединения РУ-1144 была изучена на модели артериального тромбоза сонной артерии крыс, вызванного аппликацией 50% хлорида железа (III) и модели Global Thrombosis Test (по Горогу). Оценку данного вида активности производили по удлинению времени образования тромба. Исследования влияния соединения РУ-1144 на параметр времени кровотечения проводили на мышах. В качестве препаратов сравнения использовали ацетилсалициловую кислоту, клопидогрел и ЭМГПС.Результаты. Выявленное на модели артериального тромбоза, индуцированного аппликацией хлорида железа (III), антитромботическое действие субстанции РУ-1144, превосходило таковое как у ацетилсалициловой кислоты, так и у клопидогрела в 3,5 раза, и в 2,9 раза – у ЭМГПС. На модели Global Thrombosis Test (тест Горога) in vitro соединение РУ-1144 снижало тромбогенный потенциал крови в равной степени с ацетилсалициловой кислотой и клопидогрелом. При оценивании «времени кровотечения» вещество РУ-1144 пролонгировало кровотечение в среднем в 2 раза менее выражено чем АСК и клопидогрел.Заключение. Проведенные исследования продемонстрировали у соединения РУ-1144 выраженную антитромботическую активность, превышающую таковую у ацетилсалициловой кислоты, клопидогрела и ЭМГПС, при этом способность удлинять время кровотечения была достоверно ниже, чем у препаратов сравнения.

The aim of the study was to investigate antithrombogenic properties of compound RU-1144 with previously identified pronounced antiplatelet and antioxidant activities. The thrombosis induced by Ferric chloride (FeCl3) was carried out in rats’ carotid artery, in comparison with the known antiaggregant drugs - acetylsalicylic acid (ASA) and clopidogrel, as well as with the antioxidant preparation - ethylmethylhydroxypyridine succinate (EMHPS).

Materials and methods

Materials and methods. The antithrombotic activity of compound RU-1144 was studied on the model of the rats with carotid artery thrombosis, induced by the application of 50% ferric chloride (FeCl3), and the Global Thrombosis Test model (the Görög Thrombosis Test). The evaluation of this type of activity was carried out by prolonging the time of a blood clot formation. The studies of the compound RU-1144 effect on the bleeding time parameter were performed in mice. Acetylsalicylic acid, clopidogrel and EMHPS were used as reference drugs.

Results

Results. The antithrombotic effect of the RU-1144 substance revealed in the model of arterial thrombosis induced by the application of ferric chloride (FeCl3), exceeded that of both acetylsalicylic acid and clopidogrel by 3.5 times and that of EMHPS by 2.9 times. In the model of the in vitro Global Thrombosis Test (the Görög Thrombosis Test), compound RU-1144 reduced the thrombogenic potential of the blood equally with acetylsalicylic acid and clopidogrel. The assessment of “the bleeding time”, caused by the RU-1144 substance, showed that the prolongation of bleeding was twice as less pronounced than that caused by ASA and clopidogrel.

Conclusion

Conclusion. The performed studies demonstrated a pronounced antithrombotic activity of compound RU-1144, which exceeded that of acetylsalicylic acid, clopidogrel and EMHPS, while the ability to prolong the bleeding time was reliably lower than that of reference drugs.

Abbreviations

Abbreviations: EMHPS-ethylmethylhydroxypyridine succinate; ASA - acetylsalicylic acid.

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The authors declare that there are no conflicts of interest present.