EVALUATION OF ACUTE AND SUBACUTE TOXICITY OF OIL LINIMENT BASED ON 4-((5-(DECYLTHIO)-4-METHYL-4H-1,2,4- TRIAZOL-3-YL)METHYL)MORPHOLINE

Yıl 2018, Cilt: 42 Sayı: 1, 43 - 52, 31.01.2018

Roman Shcherbyna , Volodymyr Parchenko Volodymyr Martynyshyn Vasyl Hunchak

Öz

Objective: It has now been demonstrated that compound 4-((5-(decylthio)-4-methyl-4H-1,2,4-triazol3-yl)methyl)morpholine shows antifungal and antimicrobial activities. This study was aimed to estimate
toxicity values of novel oil liniment, which is based on mentioned compound and has antifungal effect.

Material and Method: Research was held in accordance with guidelines “Toxicological screening
of new substances for animal safety products” and “Preclinical esearch of veterinary drugs”. Toxicity level
(amount of toxic doses) and benchmark doses for subacute study were assessed in conditions of acute study.
Experiments were conducted on male wistar rats using karber method.

Result and Discussion: Findings in the research of the acute effect have shown that studied substance
belongs to the group of low-toxic compounds in conditions of intragastric administration. All rats survived
and completed subacute study, and daily administration of oil liniment in duration of 14 days did not cause
possible changes in body and organ weight among animals in experimental groups. It was demonstrated that
prolonged exposure to the liniment caused possible increase of ALP and LDH on the background of possible
cholesterol decrease, which may be the evidence of cholestatic liver disease, and enhancement of
permeability of the cell membranes, which may be highlighted by destructive changes in liver.

Anahtar Kelimeler

4-((5-(decylthio)-4-methyl-4H-1, 2, 4-triazol-3-yl)methyl)morpholine, rat, toxicity

4-((5-(DESİLTİYO)-4-METİL-4H-1,2,4-TRİAZOL-3-İL)METİL)MORFOLİN ESASLI YAĞ MERHEMİ AKUT VE SUBAKUT TOKSİSİTE PARAMETRELERİ TAYİNİ

Öz

Amaç: 4-((5-(desiltiyo)-4-metil-4H-1,2,4-triazol-3-il)metil)morfolin maddesinin antifungal
ve antimikrobiyal özelliklere sahip olduğu gösterilmiştir. Bu araştırmanın amacı, bahsi geçen
bileşen esaslı antifungal etkiye sahip yağ merhemi toksisitesini tespit etmektir.

Gereç ve Yöntem: Araştırma, ‘“Toxicological screening of new substances for animal
safety products” and “Preclinical research of veterinary drugs‘da yer alan yönergelere göre
gerçekleştirilmiştir. Akut çalışma koşullarında toksisite düzeyi (toksik doz miktarı) ve subakut
çalışma için kıyaslama dozları değerlendirilmiştir. Araştırmalar, Wistar sıçanları üzerinde karber
yöntemi ile gerçekleştirilmiştir.

Sonuç ve Tartışma: Akut etkinin araştırılmasında bulgular, çalışılan maddenin intragastrik
uygulama koşullarında düşük toksik bileşikler grubuna ait olduğunu göstermiştir. Subakut
çalışmalar tamamlandı ve tüm sıçanlar sağ kurtuldu. 14 gün boyunca günlük olarak yağ liniment
uygulaması deney grupları içindeki hayvanlar ve organ ağırlığı arasında olası değişikliklere neden
olmadı. Çalışma merheme uzun süreli maruz kalmanın, kolesterol düzeyinin azalmasına neden
olabilecek ALP ve LDH'nin artışına neden olduğu ve karaciğerde yıkıcı değişikliklere sebep
olabilecek hücre zarlarının geçirgenliğinin artışına sebep olabileceğini göstermiştir.

Anahtar Kelimeler

4-((5-(desiltiyo)-4-metil-4H-1, 2, 4-triazol-3-il)metil)morfolin, toksisite, sıçan

Kaynakça

• Peyton, L.R., Gallagher, S., Hashemzadeh, M. (2015). Triazole antifungals: a review. Drugs Today (Barc), 51(12), 705-718.
• Gumber, K., Sidhu, A., Kaur, R. (2017). Sonochemical synthesis of novel magnesium 1, 2, 4-triazole-1-carbodithioate nanoparticles as antifungals. Applied Nanoscience, 7(3-4), 95-100.
• Lin, L., Liu, H., Wang, D.J., Hu, Y.J., Wei, X.H. (2017). Synthesis and biological activities of 3, 6-disubstituted-1, 2, 4-triazolo-1, 3, 4-thiadiazole derivatives. Bulletin of the Chemical Society of Ethiopia, 31(3), 481-489.
• Charney, D.S., Woods, S.W., Goodman, W.K., Rifkin, B., Kinch, M., Aiken, B., Heninger, G.R. (1986). Drug treatment of panic disorder: the comparative efficacy of imipramine, alprazolam, and trazodone. The Journal of clinical psychiatry, 47(12), 580.
• Bushueva, I., Parchenko, V., Shcherbyna, R., Safonov, A., Kaplaushenko, A., Gutyj, B., Hariv, I. (2017). Tryfuzol-new original veterinary drug. J. Fac. Pharm. Ankara/Ankara Ecz. Fak. Derg, 41(1), 42-49.
• Baum, M., Budzar, A.U., Cuzick, J., Forbes, J., Houghton, J.H., Klijn, J.G., Sahmoud, T. (2002). Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet (London, England), 359(9324), 2131-2139.
• Jakič, M., Vogler, A., Rižner, T.L. (2016). Pharmacological treatment of endometriosis: review of current and new options for treatment. Slovenian Medical Journal, 85(7-8), 410-426.
• Jarema, M., Dudek, D., Landowski, J., Heitzman, J., Rabe-Jabłońska, J., Rybakowski, J. (2011). Trazodon -the antidepressant: mechanism of action and its position in the treatment of depression. Psychiatria polska, 45(4), 611-625.
• Shcherbyna, R.О., Panasenko, O.I., Knysh, Y.G., Fotina, H.A., Vashchyk, Y.V., Fotina, T.I. (2016). The study of antimicrobial activity of 2-((4-R-3-(morpholinomethylene)-4H-1, 2, 4-triazole-5-yl) thio) acetic acid salts. Zaporozhye medical journal, (4), 97-100.
• Shcherbyna, R.O., Samura, T.O., Kyrychko, B.P., Zvenihorodska, T.V., Hyrenko, I.V. (2017). The research of ammonium 2-((4-amino-5-(morpholinomethyl)-4H-1, 2, 4-triazole-3-yl) thio) acetate (PKR-177) influence on biochemical indices in rats blood under hepatitis initiated by tetrachloride methane. Zaporozhye medical journal, 19(6), 819-822.
• Shcherbyna, R.O., Parchenko, V.V., Safonov, A.A., Bushueva, I.V., Zazharskiy, V.V., Davydenko, P.O., Borovic, I.V. (2018). Synthesis and research of the impact of new derivatives of 4-R-3 (morpholinomethyl)-4H-1, 2, 4-triazole-5-thiol on cultural attributes of pathogenic M. Bovis. Research journal of pharmaceutical biological and chemical sciences, 9(2), 70-79.
• Shcherbyna, R.O., Danilchenko, D.M., Parchenko, V.V., Panasenko, O.I., Knysh, E.H., Hromyh, N.A., Lyholat, Y.V. (2017). Studying of 2-((5-R-4-R-1-4H-1, 2, 4-triazole-3-Yl) Thio) acetic acid salts influence on growth and progress of blackberries (KIOWA Variety) propagules. Research journal of pharmaceutical biological and chemical sciences, 8(3), 975-979.
• Bihdan, O.A., Parchenko, V.V., Shcherbyna, R.O., Safonov, A.A. (2018). 1, 2, 4-Triazole Derivatives with Halogen Substituted Fragments, Their Synthesis, Modification and Biological Properties. Research journal of pharmaceutical biological and chemical sciences, 9(1), 22-29.
• Shcherbyna, R.O. (2016) The synthesis and prediction of biological activity in silico for new alkyl derivatives of 4-R-3-(morfolinometylen)-4H-1,2,4-triazole-5-thioles. Ukraïns’ kij bìofarmacevtičnij žurnal, 44, 34-38.
• Martynyshyn, V.P., Gunchak, V.M., Gutyj, B.V., Hlukh, O.S. (2017). To the method of preparation of the liniment on the basis of thiopropyl triazole and his assessment of physical properties and performance on individual microorganisms and fungi. Scientific Messenger of LNU of Veterinary Medicine and Biotechnologies, 19(82), 36-40.
• Kosenko, M.V., Malik, O.G., Kotsiumbas, I.Ya., Paterega, I.P., Chura, D.O. (1997) Toxicological control of new animal protection means: Methodical recommendations, Kiev, p.34.
• Kotsiumbas, I.Ya,, Malik, O.G., Paterega, I.P., Tishin, O.L., Kosenko, Yu.M. (2006) Preclinical studies of veterinary medicines, Triad plus, Lviv, p.360.
• Veterinary drugs. Determination of Acute Toxicity (2011). Standard of organization of Ukraine №85.2-37-736:2011. Ministry of Agrarian Policy, Kiev, p.16.
• Stefanov, O.V., Litvinova, N.V., Filonenko-Patrusheva, M.A., Frantsuzova, S.B., Khrapak, V.V. (2001) Preclinical research of medicinal products: Methodical recommendations, Avicenna, Kiev, p.528.