Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenyl)methyl)-4R-4H-1,2,4-triazole-3-yl)thio)acetic acids and its salts

From ancient times the people used different poisons as a treatment for diseases of different genesis. To date, almost nothing has changed. One of the main conditions for the development of a new drug is its low toxicity. Literature analysis has shown that 1,2,4-triazole-3-thione derivatives are low-toxic compounds and exhibit a wide range of pharmacological activities. The aim of this work was the investigate acute toxicity LC50 in vivo of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)acetate on the Zebrafish (Danio rerio) aquatic model according to OECD instruction № 203. Materials and methods. Determination of acute toxicity LC50 of the test compound was performed in vivo on a model of the aquatic organism Zebrafish (Danio rerio) according to the instruction OECD № 203 (Fish, Acute Toxicity Test) for testing chemical compounds (acute toxicity test on fish from 10.12.2009). It was used fish 2 months of age, 11.8 ± 0.1 mm long, and weighing 2.6 ± 0.2 g in the experiment. The concentration of the test compound ranged from 5.0 mg/l to 100.0 mg/l. Test water-soluble compounds were dissolved in distilled water. Each mini-aquarium with a certain dose of the compound contained at least 7 individuals of Danio rerio. During the experiments, the fish were kept on a diet for a test 96 hours and their mortality was checked every 24, 48, 72 and 96 hours. Statistical analysis of the results was performed using the program Statistica 6. Results. According to the obtained data, graphs of the dependence of the concentration on the fish mortality percentage were constructed. Then the corresponding values of LC50 sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)acetate were calculated. According to the acute toxicity of LC50 (96 hours) of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)acetate, which according to the classification of D. R. Passino and co-authors allowed it to be classified as a moderately toxic compound. Conclusions. The acute toxicity LC50 in vivo of sodium 2-((4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-yl)thio)acetate on the Zebrafish (Danio rerio) aquatic model was investigated. The research was conducted in accordance with the national “General Ethical Principles of Animal Experimentation” approved by the First National Congress on Bioethics and the “Bioethical Expertise of Preclinical and Other Animal Research”. The highest fish mortality occurs on the last day of observation (96 hours). The highest number of Zebrafish deaths is at a minimum concentration of the substance. The acute toxicity LC50 (96 hours) of the test substance was 4.5364 mg/l.

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“…To date, almost nothing has changed. One of the main conditions for the development of a new drug [1][2][3][4] is its low toxicity.…”

Section: актуальные вопросы фармацевтической и медицинской науки и прmentioning

confidence: 99%

A study of acute toxicity of newly synthesized compound on adult hydrobiont Danio rerio

Karpenko¹,

Knysh²,

Карпенко³

et al. 2021

АПФМНП

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“…A wide range of biological activity of 1,2,4-triazole derivatives (anti-inflammatory, antiviral, antitumor, immunostimulating, etc.) [1][2][3][4] and the availability of sources for their preparation determine to use this class of compounds. New derivatives based on 1,2,4-triazole are creating.…”

Section: актуальные вопросы фармацевтической и медицинской науки и пр...mentioning

confidence: 99%

Synthesis of novel 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones derivatives

Сафонов

Nevmyvaka

2020

Current Issues in Pharmacy and Medicine: Science and Practice

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A -research concept and design; B -collection and/or assembly of data; C -data analysis and interpretation; D -writing the article; E -critical revision of the article; F -final approval of the article A wide range of biological activity of 1,2,4-triazole derivatives (anti-inflammatory, antiviral, antitumor, immunostimulating, etc.) and the availability of sources for their preparation determine the prospects of using compounds of this class to create modified derivatives based on them and, as a result, medicines. Derivatives of 1,2,4-triazole have already established themselves both in the agricultural sector and in veterinary medicine and pharmacy.The aim of work was to synthesize 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones, 2-((5-(2-bromophenyl)-4-methyl-4H-1,2,4-triazole-3-yl)thio)acetic acids and their salts.Materials and methods. 3-(2-Bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones (4a-4c) were synthesized by refluxing 1 mol 2-(2-bromobenzoyl)-N-substitutedhydrazinecarbothioamides (3a-3c) with 2 mol KOH in water medium and after cooling neutralized with acetic acid. 2-((5-(2-Bromophenyl)-4-substituted-4H-1,2,4-triazole-3-yl)thio)acetic acids (5a-5c) were obtained by refluxing the solution of 0,1 mol NaOH and substances 4a-4c respectively. It was dissolved in 2-propanol medium with 0,1 mol 2-chloroacetic acid. 2-((5-(2-Bromophenyl)-4-substituted-4H-1,2,4-triazole-3-yl)thio)acetic acid salts (6a-6o) were synthesized by adding organic amines or inorganic salts to substances 5a-5c respectively in 2-propanol or water medium. The elemental analysis of synthesized compounds was established by the universal analyzer Elementar Vario L cube (CHNS). The 1H spectra (at 400 MHz and 100 MHz) were recorded in DMSO-d6 on a Varian MR-400 spectrometer and analyzed with the ADVASP™ Analyzer program. The completeness of the reactions and the individuality of the resulting compounds were controlled by the gas chromatograph Agilent 7890B with a 5977B mass spectrometry detector.Results. It was synthesized new 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thionesand there derivatives, the structure of compounds was confirmed using Elemental analysis (CHNS), 1 HNMR and Chromatographic mass spectral analysis. Conclusions. As a result, 21 novel compounds of 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones were synthesized and characterized. Синтез нових похідних 3-(2-бромфеніл)-4-заміщених-1H-1,2,4-тріазол-5(4H)-тіонів А. А. Сафонов, А. В. Невмивака Широкий спектр біологічної активності похідних 1,2,4-тріазолу (протизапальна, противірусна, протипухлинна, імуностимулювальна тощо) і доступність джерел їх отримання визначають перспективність використання сполук цього класу для створення на їхній основі модифікованих похідних, а отже і лікарських препаратів. Похідні 1,2,4-тріазолу зарекомендували себе в аграрному секторі, ветеринарії та фармації. Мета роботи -синтез 3-(2-бромфеніл)-4-заміщених-1H-1,2,4-тріазол-5(4H)-тіонів, 2-((5-(2-бромфеніл)-4-метил-4H-1,2,4-тріазол-3-іл)тіо)оцтов...

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“…Thus, there is the question of the creation of new antimicrobial medicines. 1,2,4-Triazole derivatives have already proven themselves [1][2][3][4][5][6][7][8] as compounds with low toxicity and high antimicrobial, antifungal, antiviral, hepatoprotective activity [9][10][11][12][13][14].…”

Section: Issn 2306-8094mentioning

confidence: 99%

Anti-tuberculosis activity research of 5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol

Сафонов

Zazharskyi

2019

Current Issues in Pharmacy and Medicine: Science and Practice

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Introduction. 1,2,4-Triazole derivatives have already proven themselves to be compounds with low toxicity and high antimicrobial, antifungal, antiviral, hepatoprotective activity.The aim of work is to research the anti-tuberculosis activity of 5-(thiophen-2-ylmethyl)-4H-1,2,4-triazoles-3-thiol on the bacteria strain M. bovis. Materials and methods.At the beginning of the experiment, the effect of the drug concentration and the pH of the medium on the growth rate of the culture at 37 °C was detected. M. bovis 100 passage was selected for this purpose, which was cultured at 37 °C with 5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol at the indicated concentrations in a thermostat for 3 months on medium with pH 6.5 (ten test tubes with each medicine concentration) and pH 7.1 (ten test tubes with each medicine concentration). M. bovis 100 passage was used as a control without the addition of 5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol to the medium.Results. The results of the experiment show that the effect of the drug at different concentrations on the medium with a pH 6.5 same with pH 7.1.Growth of pathogenic strain M. bovis 100 passages throughout the observation period (90 days) have been absence for all of the test (0.1 %, 0.5 % and 1.0 %) concentrations of 5-(thiophen-2-ylmethyl)-4H-1,2,4-triazoles-3-thiol.Conclusion. It can be concluded that 0.1 %, 0.5 % and 1.0 % concentration of 5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol influence on the culture properties pathogenic strain M. bovis, which cultured on the medium with pH 6.5 and pH 7.1 at 37 °C, while holding back growth, having a tuberculostatic effect. Дослідження протитуберкульозної активності 5-(тіофен-2-ілметил)-4H-1,2,4-тріазол-3-тіолуА. А. Сафонов, В. В. Зажарський Одна з основних проблем у сучасній оперативній і терапевтичній медицині та фармації -захворювання, що спричинені мікробними інфекціями.Похідні 1,2,4-тріазолів зарекомендували себе як сполуки з низькою токсичністю та високою протимікробною, протигрибковою, противірусною, гепатопротекторною активністю.Мета роботи -дослідження протитуберкульозної активності 5-(тіофен-2-ілметил)-4H-1,2,4-тріазол-3-тіолу щодо бактерії штаму M. bovis.Матеріали та методи. На початку досліду виявили вплив концентрації препарату та рН середовища на інтенсивність росту культури за температури 37 °С. Для цього відібрали M. bovis 100 пасажу, який культивували за температури 37 °С із 5-(тіофен-2-ілметил)-4H-1,2,4-тріазол-3-тіолом у зазначених концентраціях у термостаті протягом 3 місяців на середовищі з рН 6,5 (10 пробірок із кожною концентрацією препарату) та рН 7,1 (10 пробірок із кожною концентрацією препарату). Як контроль використали M. bovis 100 пасажу без додавання до середовища 5-(тіофен-2-ілметил)-4H-1,2,4-тріазол-3-тіолу.Результати. 0,1 %, 0,5 % та 1,0 % концентрації 5-(тіофен-2-ілметил)-4H-1,2,4-тріазол-3-тіолу активно впливають на культуральні властивості патогенного штаму M. bovis, що культивований на середовищі з рН 6,5 та рН 7,1 при температурі 37 °C, стримуючи ріст і розвиток, володіючи тубе...

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Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenyl)methyl)-4R-4H-1,2,4-triazole-3-yl)thio)acetic acids and its salts

Cited by 3 publications

References 6 publications

A study of acute toxicity of newly synthesized compound on adult hydrobiont Danio rerio

A study of acute toxicity of newly synthesized compound on adult hydrobiont Danio rerio

Synthesis of novel 3-(2-bromophenyl)-4-substituted-1H-1,2,4-triazole-5(4H)-thiones derivatives

Anti-tuberculosis activity research of 5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol

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