Shalai Ya. R., Mandzynets S. M., Hreniukh V. P., Finiuk N. S., Babsky A. M.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Research purpose. To study the influence of new thiazole derivative N-(5-Benzyl-1,3-thiazole-2-yl)-3,5dimethyl-1-benzofuran-2-carboxamide on the level of primary and secondary products of peroxide lipid oxidation, and superoxide radicals in the mouse Nemeth-Kellner lymphoma (NK/Ly) cells and hepatocytes. Object and research methods. Studies were performed on nonlinear male mice weighing 20-30 g. Two groups of mice were used. Mice from the first group grafted lymphoma and healthy mice from the second group were used for study of liver. The ascites form of lymphoma was passaged by intraperitonial inoculation of 10-15 million cancer cells to mice. Thiasole derivative (compound 1) was dissolved in dimethyl sulfoxide and added to the test sample (lymphoma or liver homogenate) in final concentrations of 1, 10 and 50 μM. The levels of lipid hydroperoxides, positive products of thiobarbituric acid (TBA) and superoxide radical were determined spectrophotometrically in a homogenate of lymphoma cells and liver homogenate after incubation with the drug for 10 minutes. Research results and their discussion. In the homogenate of lymphoma, the level of hydroperoxides has increased significantly by compound 1, that may indicate a damaging in the antioxidant defense system, while the hepatocyte fraction in the membrane fraction has not changed. The level of TBA-positive products has not changed in both lymphoma homogenate and in the liver homogenate. The level of superoxide radical significantly reduced in lymphoma under the influence of compound 1. Thus, the derivative of thiazole activates the processes of the formation of primary products of peroxide oxidation of lipids in the cell-lymphoma cells. At the same time, there is a significant decrease in the level of superoxide radicals. Such changes in peroxide oxidation may increase the sensitivity of lymphoma cells to antitumor drugs. Conclusions 1. In lymphoma homogenate thiazole derivative increases the level of hydroperoxides, whereas the content of TBА-positive products does not change. At the same time, the level of superoxide radicals decreases, which may indicate that compound 1 may interact with the active forms of oxygen. 2. Unlike in lymphoma cells, the presence of compound 1 in the liver homogenate does not change the level of hydroperoxides and the content of TBА-positive products. The level of the superoxide radical was slightly reduced by the action of the compound 1 only at a concentration of 10 μM. 3. Thus, the studied thiazole derivative activates the processes of the formation of primary products of lipid peroxidation in lymphoma cells and practically does not affect these processes in the healthy liver. It can be assumed that the cytotoxic action of the thiazole derivative is realized through the interaction with active forms of Oxygen. Such changes in peroxide oxidation should increase the sensitivity of lymphoma cells to antitumor compounds.

lymphoma, thiazole derivatives, free radical processes, cytotoxicity

• Horner MJ, Ries LG, Krapcho M, Neyman N, Aminou R, Howlader N. SEER Cancer Statistics Review, 1975-2006. Surveillance Epidemiology and End Rеsults (SEER). Bethesda, MD: National Cancer Institute; 2009. Available from: http://seer.cancer.gov/csr/1975_2006
• Li Z, Yang Q, Qian X. Novel thiazonaphthalimides as efficienta ntitumor and DNA photocleaving agents: Effects of intercalation, side chains, and substituent groups. Bioorg Med Chem. 2005;13(16):4864-70.
• Bilenko О, Rudenko М, Leus І, Babiy S, Skorik O, Shtemenko N. Doslidzhennia systemy hlutationu za umov halmuvannia pukhlynnoho rostu. Visnyk Lvivskoho universytetu. Ser.: Biolohichna. 2013;62:68-74. [in Ukrainian].
• Kotsiumbas IYa T-2 toksykoz ptytsi: metodychni rekomendatsii. Kyiv: Triada plius; 2004. 13 s. [in Ukrainian].
• Finiuk NS, Hreniuh VP, Ostapiuk YuV, Matiychuk VS, Frolov DA, Obushak MD, et al. Antineoplastic activity of novel thiazole derivatives Biopolym. Cell. 2017;33(2):135-46.
• Al-Saddi M, Faidallah H, Rostom S. Synthesis and biological evaluation of some 2,4,5-trisubstituted thiazole derivatives as potential antimicrobial and anticancer agents. Arch Pharm Sci. 2008;341(7):424-34.
• Carter PH, Scherle PA, Muckelbauer JK, Voss ME, Liu RQ, Thompson LA, et al. Photochemically enhanced binding of small molecules to the tumor necrоsis factor receptor-1 inhibits the binding of TNF-alpha. Proc Natl Acad Sci. 2001;98(21):11879-84.
• Clarkson RM, Moule AJ, Podlich HM. The shelf-life of sodium hypochlorite irrigating solutions. Australian Dental Journal. 2001;46(4):269-76.
• Degterev A, Lugovskoy A, Cardone M, Mulley B, Wagner G, Mitchison T, et al. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat Cell Biol. 2001;3(2):173-82.
• Dos Santos TA, da Silva AC, Silva EB, Gomes PA, Espíndola JW, Cardoso MV, et al. Antitumor and immunomodulatory activities of thiosemicarbazones and 1,3-Thiazoles in Jurkat and HT-29 cells. Biomedicine & Pharmacotherapy. 2016;82:555-60.
• Geronikaki A, Eleftheriou P, Vicini P, Alam І, Dixit А, Saxena АК. 2-Thiazolylimino/Heteroarylimino-5-arylidene-4-thiazolidinones as New Agents with SHP-2 Inhibitory Action. Med. Chem. 2008;51(17):5221-8.
• Kok S, Gambari R, Chui C, Yuen MC, Lin E, Wong RS. Synthesis and anti-cancer activity of benzothiazole containing phthalimide on human carcinoma cell lines. Bioorg. Med. Chem. 2008;16(7):3626-31.
• Turov KV, Krupska TV, Barvinchenko VM. Antyradykalni vlastyvosti pokhidnykh tiazolu. Vplyv na metabolichnu aktyvnist drizhdzhiv Biotechnologia Acta. 2012;5(3):75-83. [in Ukrainian].
• Hubskyi YuI. Metody otsinky antyoksydantnykh vlastyvostei fiziolohichno aktyvnykh spoluk pry initsiiuvanni vilnoradykalnykh protsesiv u doslidakh in vitro: metodychni rekomendatsii. Derzh. farm. tsentr MOZ Ukrainy. Kyiv; 2002. 26 s. [in Ukrainian].
• Lowry OH. Protein measurement with the Folin phenol reagent. Journal of Boilogical Chemistry. 1951;193(1):404-15.
• Myronchyk VV. Sposob opredelenyia hydroperekysei lypydov v byolohycheskykh tkaniakh. A. S. № 1084681 SSSR, MKI; 1984. 8 s. [in Russian].
• Timirbulatov RR, Seleznev EI. Metod povyisheniya intensivnosti svobodnoradikalnogo okisleniya lipidosoderzhaschih komponentov krovi i ego diagnosticheskoe znachenie. Lab. delo. 1981;4:209-11. [in Russian].
• Denisenko SV, Kostenko VA. Izmeneniya produktsii aktivnyih form kisloroda v semennikah belyih kryis v usloviyah hronicheskoy intoksikatsii nitratom natriya. Sovr. probl. toksikologii. 2002;4:44-6. [in Russian].

«Bulletin of problems biology and medicine» Issue 1 Part 2 (143), 2018 year, 234-238 pages, index UDK 577.35+577.352

10.29254/2077-4214-2018-1-2-143-234-238