Anticonvulsant activity 2-((5-(3-(4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)-thio)-1-arylethanone

Authors

  • O. A. Bihdan Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2019.3.184183

Keywords:

anticonvulsants, 2-((5-(3-, 4-fluorophenyl)-4-R2-1, 2, 4-triazol-3-yl)tio)-1-aryletanones, “structure – action”

Abstract

 

The aim of work is to study of the anticonvulsant activity of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)thio)-1-aryletanones, the establishment of some laws between the structure of compounds and their activity.

Materials and methods. The study of the anticonvulsant activity of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)thio)-1-aryletanones was carried out according to the test of interaction with agents that excite the central nervous system. The experiments were performed on the intact white rats of the Vistar line, weight 160–190 g, five animals in each group. As convulsive models, corazole-induced convulsions were used, which was caused by subcutaneous administration of corazole at a dose of 100 mc/kg.

Then the animals were placed in individual transparent flexiglaz cameras and watched them for one hour. Six indicators of convulsions were recorded: the latent period, the number of animals with generalized clonic or tonic-clonic convulsions in the group, the number of animals with tonic extension, mortality and life expectancy.

Results. The resulting compounds exhibit high anticonvulsant activity. So, against the background of the introduction of 2-((5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-yl)thio)-1-(3-fluorophenylethanone), 2-((5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-yl)thio)-1-(4-fluorophenylethanone) and 2-((5-(4-fluorophenyl)-4-methyl-1,2,4-triazole-3-yl)thio)-1-(4-fluorophenylethanone), the latent period of the onset of convulsions under the influence of corazole increases by 57.1 %, 67.3 % and 28.6 %, respectively (P < 0.05 ), and the duration of convulsions is reduced by 33.4 %, 31.5 % and 38.9 %, respectively (P < 0.05), which indicates the neuroprotective and membrane stabilizing effect of the corresponding 2-((5-(3-4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)thio)-1-aryletanones. Comparison preparations of midocalm and phenobarbital increase the latent period of the onset of convulsive reactions by 51.0 % and 34.7 % at (P < 0.05), and the duration of convulsions decreased by 20.4 % and 14.9 % at (P < 0.05) respectively.

Conclusions. The anticonvulsant activity of some 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)thio)-1-aryletanones was studied for the first time on a model of corazole convulsions. Three active compounds are 2-((5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-yl)thio)-1-(3-fluorophenylethanone), 2-((5-(3-fluorophenyl)-4-amino-1,2,4-triazole-3-yl)thio)-1-(4-fluorophenylethanone) and 2-((5-(4-fluorophenyl)-4-methyl-1,2,4-triazole-3-yl)thio)-1-(4-fluorophenylethanone). In some cases, regularities were revealed between the structure of molecules and their activity.

 

References

Bihdan, O. A. (2019). Fizyko-khimichni vlastyvosti 2-((5-(3-,4-ftorfenil)-4-R2-1,2,4-triazol-3-il)tio)-1-aryletanoniv ta yikhnikh vidnovlenykh system [Physical-chemical properties of 2-((5-(3-,4-fluorophenyl)-4-R2-1,2,4-triazol-3-il)tio)-1-arylethanons and their reduced systems]. Current issues in pharmacy and medicine: science and practice, 2, 116 122. doi: 10.14739/2409-2932.2019.2.170972 [in Ukrainian].

Bihdan, O. A., Panasenko, O. I. Knysh, Je. G.  Parchenko, V. V. (2016). Doslidzhennja reakcij heterotsyklizatsii 3-tio- ta 3-tio-4- aminopokhidnykh 1,2,4-triazolu [Heterocyclization reactions study of 3-thio and 3-thio-4-amino derivatives of 1,2,4–triazole]. Current issues in pharmacy and medicine: science and practice, 1, 90-97. doi: 10.14739/2409-2932.2016.1.62048 [in Ukrainian].

Kaplaushenko, A. H., Panasenko, T. O., Knysh, Ye. H., Panasenko, O. I., Samura, B. A., & Shykova V. V. (2008). Vyvchennia vplyvu 5-R1-4-R2-1,2,4-3-tioniv ta yikh S-pokhidnykh na tryvalist etaminalnatriievoho snu [Study of the influence of 5-R1-4-R2-1,2,4-3-thiones and their S-derivatives on the duration of ethaminic sodium]. Zaporozhye medical journal, 6, 75-78. [in Ukrainian].

Mashkovskij, M. D. (2000). Lekarstvennye sredstva [Medicines]. Vol. 1. Moskva [in Russian].

-[5-(furan-2-il)-4-fenil-4N-1,2,4-tryazol-3-iltio]-1-(4-khlorfeniletanon), yakyi proiavliaie protysudomnu aktyvnist. pat. 16835 Ukraina [2-[5-(furan-2-yl)-4-phenyl-4h-1,2,4-triazol-3-ylthio]-1-(4-chlorophenylethanon), revealing an anticonvulsant activity. pat. 16835 ] / Knysh, Je. G., Parchenko, V. V., Panasenko, T. O., Samura, I. B., Litovchenko, A. L.  Samura, B. A.; № u200603321 ; zaiavl. 27.03.06 ; opubl. 15.08.06, biul. 8. [in Ukrainian].

Parchenko, V. V. (2006). Syntez, fizyko-khimichni ta biolohichni vlastyvosti pokhidnykh 1,2,4-triazol-3-tionu, yaki mistyat yadro furanu. (Dis… kand. farm. nauk). [Synthesis, physical, chemical and biological properties of derivatives of 1,2,4-triazole-3-thione containing the core of furan. Dr. farm. sci. diss.]. Kyiv. [in Ukrainian].

Martynyshyn, V. P., Hunchak, V. M., Yaroshenko, А. І.,  Parchenko, V. V. (2019). Chromagraphic research of liniment, which active substance belongs to new derivatives of 1, 2, 4-triazole. Research Journal of Pharmaceutical, Biological and Chemical Sciences, Vol. 10. Issue 1. P. 806-811. doi: 10.13140/RG.2.2.35871.61609.

Parchenko, V. V. (2014). Syntez, peretvorennia, fizyko-khimichni ta biolo¬hichni vlastyvosti v riadi 5-furylzamishchenykh 1,2,4-triazol-3-tioniv (Dis. dokt. farm. nauk). [Synthesis, transformation, physico-chemical and biological properties in the number of 5-furylsubstituted 1,2,4-triazole-3-thiones Dr. farm. sci. diss.]. Zaporizhzhia. [in Ukrainian].

Shcherbyna, R., Parchenko, V., Martynyshyn, V.,  Hunchak, V. (2018). Evaluation of acute and subacute toxicity of oil liniment based on 4-((5-(decylthio)-4-methyl-4h-1,2,4triazol-3-yl)methyl)morpholine. J. Fac. Pharm. Ankara, 42(1), 43-52. doi: 10.1501/eczfak_0000000601

Bihdan, O., Gotsulya, A., Parchenko, V.,  Izhboldin, O. (2019). Influence of different determination of 1,2,4-triazols on the growth, development and yield of grain sorghum. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 10(2), 1156-1160.

Bihdan, O., Parchenko, V., Zazharskyi, V., Fotina, T.,  Davydenko P. (2018). Influence Of 3-(3-Fluorophenyl)-6-(4-Methoxyphenyl)-7H-[1,2,4]-Triazolo-[3,4-B][1,3,4]Thiadiazine On The Cultural Properties Of Pathogenic Mycobacterium Bovis. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 9(6), 166-170.

Bihdan, O., Parchenko, V.,  Zazharskyi, V. (2019). Studying of physico-chemical properties of 5-(2-,3-fluorophenyl)-4-((aryl-, geteryl) yliden) amino-1,2,4-triazole-3-thiols and any of their retrievalproducts. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 10(1), 464-474.

Bihdan, O., Parchenko, V. (2018). Some aspects of synthesis 3-(2-florphenyl)-6-r1-[1,2,4]triazol[3,4-b] [1,3,4] thiadiazole and 3-(2-, 3-ftorphenyl)-6- r2-7 h [1,2,4] triazolo [3,4-b] [1,3,4] tiadiazines. Research Journal of Pharmaceutical, Biological and Chemical Sciences. 9(3), 463-470.

Shcherbyna, R., Danilchenko, D., Parchenko, V., Panasenko, O., Knysh, Ye., Hromyh, N.,  Lyholat, Yu. (2017). Studying of 2-((5-r-4-r1-4h-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.

Shcherbyna, R., Parchenko, V., Varynskyi, B., & Kaplaushenko, A. (2019). The development of HPLC-DAD method for determination of active pharmaceutical ingredient in the potassium 2-((4-amino-5-(morpholinomethyl)-4H-1,2,4-triazol-3-yl)thio) acetate substance. Current Issues In Pharmacy And Medical Sciences, 32(1), 5-9. doi: 10.2478/cipms-2019-0001

How to Cite

1.
Bihdan OA. Anticonvulsant activity 2-((5-(3-(4-fluorophenyl)-4-R2-1,2,4-triazole-3-yl)-thio)-1-arylethanone. Current issues in pharmacy and medicine: science and practice [Internet]. 2019Nov.21 [cited 2024Jul.21];(3). Available from: http://pharmed.zsmu.edu.ua/article/view/184183

Issue

Section

Original research