Determination cytotoxicity of [1,2,4]triazolo[4,3-a]-pyrazine derivatives
Keywords:[1, 2, 4]triazolo[4, 3-а]pyrazines, cytotoxicity, cytotoxic concentration, test system CellTiter-Glo, cell culture, tubertsydyn, taxol
With test systems CellTiter-Glo was determined the cytotoxicity of series N7-aryl/benzyl-3-tioxo-2,3-dihydro-7Н-[1,2,4]triazolo-[4,3-а]pyrazin-8-ones, their 3-S- acetamides and 3-S-benzyl derivatives. The synthesis of the compounds performed based on the previously developed and published scheme. Structure and purity of the compounds proved with 1H-NMR and element analysis.
Methods. The method is based on determining the number of viable cells in culture by intensity of luminescence mixture of cell suspension of prostate cancer Du145, solution of the substance and CellTiter-Glo reagent. Tubercidin and taxol were used as reference drugs. The parameter СK50, that has been set according to a study, describes the ability of analyzed substances induce cell death.
Results. Cytotoxic concentration of synthesized 3-substituted N7-aryl/benzyl-2,3-dihydro-7Н-[1,2,4]triazolo-[4,3-а]pyrazine-8-ones not exceed the maximum concentration of compounds, which were tested, and was above 30 mkM. This demonstrates the complete absence of negative impact of these substances on cells of prostate cancer Du145.
Conclusions. Found that these compounds do not exhibit toxic effects on living cells, making the actual possibility of developing new effective and safe drugs on their base. Also inappropriate to search anticancer drugs among of the N7-aryl/benzyl-2,3-dihydro-7Н-[1,2,4]triazolo-[4,3-а]pyrazine-8-one derivatives
Order of the Ministry of Health of Ukraine №944 of 14.12.2009 «On approval of the pre-clinical study of medicinal products and expert evaluation of pre-clinical study of medicinal products». Available at: http://zakon5.rada.gov.ua/laws/show/z0053-10
Clemedson, С., McFarlane-Abdulla, E., Andersson M. et. al. (1996). MEIC evaluation of acute systemic toxicity. ATLA (Alternatives to Laboratory Animals), 251–311.
Chervonskaya, H. P. (1998). Kul'tura kletok – al'ternatyvnaya byolohycheskaya model' v toksykolohycheskykh yssledovanyyakh [Cell culture – alternative biological model in toxicology studies]. Abstracts of the 1st Russian Congress of Toxicologists (Moscow), 328.
Dyadyshchev, N. R., Rybalkyn, S. P., Marchenko, A. Y. (1998). Byolohycheskye modely in vitro v toksykolohyy [Biological in vitro model in toxicology]. Abstracts of the 1st Russian Congress of Toxicologists (Moscow), 276.
Eropkyn, M. Yu., Eropkyna, E. M. (2003). Kul'tury kletok kak model'naya systema yssledovanyya toksychnosty y skrynynha tsytoprotektornykh preparatov [Cell cultures as a model system toxicity studies and screening of cytoprotective drugs]. St. Petersburg: Morsar AB, 239.
Botham, P., Lewis, R. (1996). Development of in vitro techniques for irritancy testing. Human and Experimental Toxicology, 15 (2), 141.
Hurna, E. (1997). In vitro metody a ich vyuzitie v toxikologii [In vitro methods and their use in toxicology].Veterinary medicine, 42 (7), 213–215.
Combes, R., Balls, M. (2001). Ethical investment what is it, and what are the implications for industry funding of research into alternatives? ATLA, 29 (1), 55–62.
Hartung, T., Gstraunthaler, G., Coecke, S. et. al. (2001). Good cell culture practice (GCCP) – an initiative for standardization and quality control of in vitro studies. The establishment of an ECVAM Task Force on GCCP. ALTEX, 18 (1), 75–78.
Danlybaeva, H. A., Zhylkybaev, A. A., Rikov, V. A. et. al. (2012). Tsytotoksychnost' karboranylsoderzhashchykh soedynenyy [The cytotoxicity of carbonyl compounds]. Biotechnology. Theory and practice, 3, 49–53.
Kulykovskaya, K. Yu., Kovalenko, S. S., Drushlyak A. H. y dr. (2014). Cyntez proyzvodnykh N7-aryl[1,2,4]tryazolo[4,3-a]pyrazyn-3,8(2H,7H)-dyonov y ykh 3-tyoksoanalohov kak potentsyal'nykh farmatsevtycheskykh ahentov [Synthesis of N7-aryl[1,2,4]triazolo[4,3-a]pyrazine-3,8(2H,7H)-dione derivatives and 3-tioksoanalogues as potential pharmaceutical agents]. Bulletin KazNMU, 5, 132–136.
Kovalenko, S. S., Kulikovska, K. Yu., Drushlyak, O. G. et al. (2014). A suitable synthesis of [1,2,4]triazolo[4,3-a]pyrazin-8(7H)-one derivatives. Chemistry of Heterocyclic Compounds, 8, 1243–1249.
Copyright (c) 2015 Ірина Олександрівна Журавель, Кристина Юріївна Куликовська
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.
Authors, who are published in this journal, agree to the following conditions:
1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons CC BY, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.
2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.