EFFECT OF 2-[3-BROMO-1-(THIETANYL-3)-1,2,4-TRIAZOLYL-5-THIO]ACETIC ACID POTASSIUM SALT ON THE HEMOSTATIC SYSTEM

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DOI: https://doi.org/None
Issue: 
6
Year: 
2017

Professor, Academician of the Russian Academy of Sciences V.G. Kukes (4), MD; Professor N.B. Lazareva (4), MD; Professor D.B. Nikityuk (3), MD, Corresponding Member of the Russian Academy of Sciences; Professor A.L. Urakov (1, 2, 3), MD; A.V. Samorodov (1, 2), MD; Professor F.Kh. Kamilov (2), MD; Professor E.E. Klen (2), PhD; Professor F.A. Khaliullin (2), PhD 1-Izhevsk State Medical Academy; 281, Communards St., Izhevsk 426034, Russian Federation; 2-Bashkir State Medical University; 3, Lenin St., Ufa 450000, Russian Federation; 3-Federal Research Center of Nutrition, Biotechnology, and Food Safety; 2/14, Ustyinsky Proezd, Moscow 109240, Russian Federation; 4-I.M. Sechenov First Moscow State Medical University; 8, Trubetskaya St., Build. 2, Moscow 119991, Russian Federation

Introduction. Earlier investigations of synthesized derivatives of nitrogen-containing heterocycles have demonstrated that some representatives of this series have pronounced antiplatelet activity. An in vitro experiment has established the high efficacy of 2-[3-bromo-1-(thietanyl-3)-1,2,4-triazolyl-5-thio]acetic acid (compound I) potassium salt as an agent for preventing thrombosis. Objective: to conduct a preclinical study of the in vivo effect of compound I on the hemostatic system. Material and methods. Investigations were performed in outbred mature male albino rats aged 3.5–4.0 months, weighing 150-200 g. Pentoxifylline was used as a drug of comparison. The test compound and its analogue were intraperitoneally administered to the animals. Platelet-rich and platelet-free plasma samples were obtained by citrate blood centrifugation. The overall trend of coagulation, the functional activity of platelets and fibrinogen, the activity of fibrinolysis, and the physicomechanical properties of the clots formed were determined. The clotting time of whole venous blood was recorded using the Sukharev method. A TEG 5000 thromboelastograph hemostasis device, a Biola 230LA platelet aggregation analyzer, a selective STA-Compact hemostasis analyzer, and a ThermoTracer TH9100XX thermal imaging camera were applied. The normal distribution of the actual data was checked using the Shapiro-Wilk test. The median and interquartile ranges were employed to describe the groups. Analysis of variance was carried out using the Kruskal-Wallace test. Results. 2-[3-Bromo-1-(thietanyl-3)-1,2,4-triazolyl-5-thio]acetic acid potassium salt was ascertained to be superior to pentoxifylline in the spectrum and level of anti-aggregation activity. Conclusion. The preclinical studies of the effect of the novel 2-[3-bromo-1-(thietanyl-3)-1,2,4-triazolyl-5-thio]acetic acid potassium salt on the hemostatic system confirmed its potential efficacy as an anti-aggregation agent for preventing thrombosis.
Keywords: 
3-thiethanyl-substituted triazole derivatives
hemostatic system
anti-aggregation activity
References: 
  1. Samorodov A.V., Kamilov F.Kh. Khaliullin F.A. Shabalina Y.V., Khalimov A.R. Murataev D.Z. Antithrombotic effect of new cyclohexilammonium salt 2-[1-ethyl-3-methyl-7-(dioxothietanyl-3)xanthinyl-8-thio]acetic acid on experimental venous thrombosis. 7th European Congress of Pharmacology (EPHAR2016), Congress Book 2016; 167.
  2. Samorodov A., Kamilov F., Timirkhanova G., Samorodova A., Khaliullin F., Murataev D. Antithrombotic activity of new 1-ethylxanthine cyclohexylammonium salt. Federation of American Societies for Experimental Biology Journal, 2014; 28: 1054.5.
  3. Klen E.E`., Haliullin F.A., Spasov A.A., Makarova N.N., Bagautdinova L.F., Naumenko L.V. Sintez i gemoreologicheskie svoystva novyh proizvodnyh 1,2,4-triazola. Himiko-farmacevticheskiy zhurnal, 2008; 42 (9): 15-17. [Klen E.E ., Khaliullin F.A., Spasov A.A., Makarova N.N., Bagautdinova L.F., Naumenko L.V. Synthesis and rheological properties of new derivatives of 1,2,4-triazole. Himiko-farmatsevticheskiy zhurnal, 2008; 42 (9): 15–7 (in Russian)].
  4. Samorodov A.V., Kamilov F.H., Halimov A.R., Klen E.E`., Haliullin F.A. Vliyanie novoy kalievoy soli na osnove 3-tietanilzameshhennogo triazola na sistemu gemostaza. Biomedicina, 2016; 3: 59–67. [Samorodov A.V., Kamilov F.Kh., Khalimov A.R., Klen E.E., Khaliullin F.A. The effect of the new potassium salt based on 3-triazole diethanolamine on hemostasis. Viomedicina, 2016; 3: 59–67 (in Russian)].
  5. Rukovodstvo po provedeniyu doklinicheskih issledovaniy lekarstvennyh sredstv. Chast` 1. M.: Grif i K, 2012; 944. [The guidelines for preclinical studies of pharmaceuticals. Part 1. Moscow: Grif i K, 2012; 944 (in Russian)].
  6. Kishkun A.A. Rukovodstvo po laboratornym metodam diagnostiki. M.: GE`OTAR-Media, 2002; 346. [Kishkun A.A. A manual of laboratory methods for diagnosis. Moscow: GEOTAR-Media, 2002; 346 (in Russian)].
  7. Urakov A.L., Kasatkin A.A., Urakova N.A., Ammer K. Infrared thermographic investigation of fingers and palms during and after application of cuff occlusion test in patients with hemorrhagic shock. Thermology International, 2014; 24 (1): 5–10.
  8. Urakov A.L., Urakova N.A., Kasatkin A.A. Thermal imaging improves the accuracy hemorrhagic shock diagnostics: The concept and practical recommendations. LAP LAMBERT Academic Publishing, 2016; 60.
  9. Trental®. Product monography. Sanofi-aventis Canada Inc., 16.12.2008. [Electronic resource].Mode of access: http://www.sanofi.ca/products/en/trental