DOI: https://doi.org/10.22263/2312-4156.2022.4.89
O.G. Sechko, V.M. Tsarenkov
The assessment of acute toxicity of 3-[4-(2-fluorobenzoyl)piperazine-1-carbonyl]-N-[3-(trifluoromethyl)-phenyl]benzamide
Belarusian State Medical University, Minsk, Republic of Belarus
Vestnik VGMU. 2022;21(4):89-99.
Abstract.
Objectives. To evaluate the acute toxicity of a benzamide derivative – 3-[4-(2-fluorobenzoyl)piperazine-1-carbonyl]-N-[3-(trifluoromethyl)-phenyl]benzamide after a single intragastric administration to laboratory mice and rats.
Material and methods. Acute toxicity was assessed in experiments on 48 clinically healthy CBA mice of both sexes and 48 clinically healthy Wistar rats of both sexes. The compound under study was administered intragastrically as an aqueous suspension at doses 100 mg/kg, 500 mg/kg and 2000 mg/kg of body weight. The observation duration of intoxication pattern after administration made up 14 days. Changes in body weight of the rodents were determined, autopsy was performed, macroscopic analysis was made, and the weight of the heart, liver, lungs, spleen, and kidneys was determined. The toxicity class of the compound under study was determined by the value of half-lethal dose (LD50).
Results. During the experiment, the death of animals was not observed. The general condition of all animals was satisfactory. In each of the experimental groups of mice and rats on days 2, 7 and 14 of the experiment, a statistically insignificant increase in body weight was observed compared to the control group (p>0.05), except for male rats of group №2 (dose 500 mg/kg) – this group had a statistically significant increase in body weight (p<0.05). Macroscopic examination did not reveal any negative effect of the benzamide derivative on the internal organs.
Conclusions. LD50 is over 2000 mg/kg. Thus, the benzamide derivative has been assigned to the 5th class of toxicity according to the modified classification of the Organisation for Economic Co-operation and Development (OECD) – almost non-toxic compound and to the 5th class of toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) – i.e., it possesses relatively low acute toxicity. The LD50 of the benzamide derivative is significantly higher than the LD50 of isoniazid (170 mg/kg intragastrically in mice), which characterizes the benzamide derivative as a less toxic compound.
Keywords: anti-tuberculosis activity, acute toxicity, benzamide derivative, 3-[4-(2-fluorobenzoyl)piperazine-1-carbonyl]-N-[3-(trifluoromethyl)-phenyl]benzamide.
References
1. Garrido-Cardenas JA, de Lamo-Sevilla C, Cabezas-Fernández MT, Manzano-Agugliaro F, Martínez-Lirola M. Global tuberculosis research and its future prospects. Tuberculosis (Edinb). 2020 Mar;121:101917. doi: http://dx.doi.org/10.1016/j.tube.2020.101917. Epub 2020 Feb 23.
2. World Health Organization. 2020 Antibacterial agents in clinical and preclinical development: an overview and analysis. Geneva; 2021. Available from: https://www.who.int/publications/i/item/9789240021303. [Accessed 18th Jule 2022].
3. World Health Organization. Global tuberculosis report 2020. Geneva; 2020. Available from: https://www.who.int/publications/i/item/9789240013131. [Accessed 18th Jule 2022].
4. World Health Organization. Global Strategy for TB Research and Innovation (WHA73.3): Seventy-third World Health Assembly. Geneva; 2020. Available from: https://apps.who.int/gb/ebwha/pdf_files/WHA73/A73_R3-en.pdf. [Accessed 18th Jule 2022].
5. Sechko OG, Slabko IN, Tcarenkov VM. Antituberculosis activity of benzamide and benzoic acid derivatives. V: M-vo zdravookhraneniya Resp Belarus', Belorus gos med un-t; Rubnikovich SP, Filonyuk VA, red. BGMU v avangarde meditsinskoi nauki i praktiki: rets ezhegod sb nauch tr. Minsk, RB; 2021. Vyp 11. Р. 540-6. (In Russ.)
6. Griffiths PA, Babb JR, Fraise AP. Mycobacterium terrae: a potential surrogate for Mycobacterium tuberculosis in a standard disinfectant test. J Hosp Infect. 1998 Mar;38(3):183-92. doi: http://dx.doi.org/10.1016/s0195-6701(98)90273-0
7. Mamylina NV. Analysis of behavioral activity of experimental animals undergoing emotional pain stress. Sovrem Problemy Nauki Obrazovaniya. 2011;(5). Available from: https://science-education.ru/ru/article/view?id=4922. [Accessed 18th Jule 2022]. (In Russ.)
8. Grzhibovskii AM, Ivanov SV, Gorbatova MA. Comparison of quantitative data from three or more independent samples using Statistica and SPSS software: parametric and nonparametric criteria. Nauka Zravookhranenie. 2016;(4):5-37. (In Russ.)
9. Isoniazid. Tuberculosis (Edinb). 2008 Mar;88(2):112-6. doi: http://dx.doi.org/10.1016/S1472-9792(08)70011-8
Information about authors:
O.G. Sechko – Master of Pharmaceutical Sciences, postgraduate, senior lecturer of the Chair of Pharmaceutical Technology, Belarusian State Medical University, https://orcid.org/0000-0001-5727-9936
E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Olga G. Sechko;
V.M. Tsarenkov – Doctor of Pharmaceutical Sciences, professor of the Chair of Pharmaceutical Technology, Belarusian State Medical University, https://orcid.org/0000-0001-8724-7273
