Synthesis, physical and chemical properties, antihypoxic activity of some 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl]-4-R1-4H-1,2,4-t

Authors

  • V. M. Odyntsova Zaporizhzhia State Medical University, Ukraine,
  • Ye. G. Knysh Ye. G., Zaporizhzhia State Medical University, Ukraine,
  • O. I. Panasenko Zaporizhzhia State Medical University, Ukraine,

DOI:

https://doi.org/10.14739/2409-2932.2018.1.123590

Keywords:

1, 2, 4-triazole, infrared spectroscopy, NMR-H-spectroscopy, gas chromatography-mass spectrometry

Abstract

Today, an increase of natural and technogenic situations leads to the disorders of the central nervous system, functional-metabolic processes, vascular diseases, in particular, acute cerebral blood flow disorders. In addition, the changes occurring on the molecular and cellular levels are in the basis of the functional violations of individual systems and the organism as a whole. Hypoxia not only complicates the disease course, but in most cases, determines its outcome. The important role in the fight against hypoxia belongs to antioxidants, which improve the circulating oxygen utilization by the body, reduce its need for the organs and tissues, which is not only expedient but necessary for the treatment of many acute and chronic pathological processes. So, the frequency of the hypoxic states and a wide range of factors causing them determine the relevance of new ways and methods finding to overcome the oxygen deficiency.

The aim of this work is the purposeful search of some 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl]-4-R1-4H-1,2,4-triazole-3-thiols, the study of their physical and chemical properties and pharmacological screening of the antihypoxic activity of the obtained compounds.

Materials and methods. The study of physical and chemical properties was conducted on certified and licensed modern equipment. Antihypoxic activity was studied during the modeling process of hypoxia with hypercapnia. Mexidol was used as a comparison drug in studies at a dose of 100 mg/kg.

Results. As the result of the study, it was found that the synthesized compounds and the comparison drug influenced on rats’ life span differently. Compounds, the antihypoxic activity of which exceeded control have been discovered, and others’ were at the level of Mexidol. A number of compounds showed a somewhat less activity in comparison with control, and two compounds, among the investigated ones were weaker then comparison drug action, but they did not reduce the life expectancy of the investigated groups in comparison with control. The effect of the remaining compounds on the lifetime of the investigated group was at the level of control group that received the physiological solution.

Conclusions. A series of new compounds of derivatives among 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazol-3-yl)thio)methyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-(5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl)-4-R1-4H-1,2,4-triazole-3-thiols have been synthesized, the structure of which has been confirmed with the help of modern physical and chemical methods of analysis. The most active compounds among the studied ones were 3a and 2a, their antihypoxic activity exceeds control on 37.86 % and 36.30 % and Mexidol is on 7.35 % and 5.79 % respectively.

References

Sejfulla, R. D. (2001). Sportivnaya farmakologiya [Sports pharmacology]. Мoscow: Moskovskaya pravda. [in Russian].

Stratienko, Ye. N. (1998). Farmakologichieskaya kоrrekciya fizicheskoj rabotosposobnosti v usloviyakh gipobarichieskoj gipoksii [Pharmacological correction of physical health capacity of hypobaric hypoxia]. Voennyj medicinskij zhurnal, 2, 31–32. [in Russian].

Shakhmardanova, S. A., Maximov, M. L., Parshina, L. N., Trofimov, B. A., Tarasov, V. V., Chubarev, V. N., et al. (2017). Pharmacological Correction of Hypoxic Conditions by Complexes of Zinc with N-Alkenylimidazoles. BioNanoSci, 7(2), 338–339.

Voronina, T. А. (2001). Antioksidant meksidol. Osnovnye nejropsikhotropnye e’ffiekty i mekhanizm dejstviya [Antioxidant Mexidol. Thebasic neuropsychotropic effects and mech anism of actio]. Psikhofarmakologiya i biologichieskaya narkologiya, 1, 2–12. [in Russian].

Kovalenko, V. N. (Eed) (2017) Kompendium. Lekarstvennye preparaty [Drugs]. Kyiv: MORION. [in Russian].

Pruglo, E. S., Odintsova, V. M., Safonov, A. A., Samura, B. A., Panasenko, O. I., Knysh, E. G., & Bezugly, P. A. (2013) Antyhipoksychna aktyvnist alkilpokhidnykh 5-(adamantan-1-il)-4-R-1,2,4-triazol-3-tionu [Antihypoxic activity of alkil derivatives of 5-(adamantane-1-yl)-4-R-1,2,4-triazole-3-thione]. Zaporozhye medical journal, 3, 98–100. [in Ukrainian]. doi: https://doi.org/10.14739/2310-1210.2013.3.13653.

Odintsova, V. M., Pruglo, Ye. S., Gotsulya, A. S., Panasenko, O. I., & Knysh, Ye. G. (2014) Antyhipoksychna aktyvnist solei 2-(5-(adamantan-1-il)-4H-1,2,4-triazol-3-iltio)atsetatnykh kyslot [Antihypoxic activity of salts of (2-(5-(adamantane-1-yl)-4H-1,2,4-triazole-3-ylthio) acetate acids]. Zaporozhye medical journal, 2(83), 94–96. [in Ukrainian]. doi: https://doi.org/10.14739/2310-1210.2014.2.25440.

Knysh,Ye. H., Panasenko, O. І., Pruhlo, Ye. S., Odyntsova, V. M. & Safonov, A. A. (2016). Patent 111228 Ukraina, МPК 51 А61К 31/4196 (2006.01), С07D 249/12 (2006.01). 2-((5-(adamantan-1-il)-4-fenil-4H-1,2,4-tryazol-3-il)tio)-N-(4-ftorbenzyliden)atsetohidrazyd, yakyi proiavliaie antyhipoksychnu aktyvnist [Patent 111228 Ukraine, МПК51 А61К 31/4196 (2006.01), С07D 249/12 (2006.01). 2-(5– (adamantan-1-yl) -4-phenyl-4H-1,2,4-triazol-3-yl) thio) -N ‘– (4-fluorobenzylidene) acetohydrazide, which exhibits antihypoxic activity]. Biulleten, 7. [in Ukrainian].

Knysh,Ye. H., Panasenko, O. І., Pruhlo, Ye. S., Safonov, A. A., Odyntsova, V. M., Bihdan, O. A., et al. (2014) Patent 92681 Ukraina, МPК 51 (2014.01) С 07 D 249/00, А 61 К 31/00. Pokhidni 1,2,4-tryazol-3-tionіv, yaki proiavliaut antyhipoksychnu аktyvnist [Patent 92681 Ukraine, IPC51 (2014.01) C 07 D 249/00, A 61 K 31/00. Derivatives of 1,2,4-triazole-3-thione that exhibit antihypoxic activity]. Biulleten, 16. [in Ukrainian].

Suhak, O. А., Panasenko, А. І., & Knysh, Ye. G. (2017) Antyhipoksychna aktyvnist benzylidenhidrazydiv 4-R-5-(tiofen-2-ilmetyl)-1,2,4-triazol-3-il)tiootstovoi kysloty [Antihypoxic activity of benzylidenhydrazides of 4-R-5– (thiophene-2-ylmethyl)-1,2,4-triazol-3-il)thioacetic acid]. Current issues in pharmacy and medicine: science and practice, 2(24), 147–151 [in Ukrainian]. doi: 10.14739/2409-2932.

2.103531.

Odyntsova, V. M., & Pruglo Ye. S. (2015) Synthesis, physico-chemical properties and the study of anti-hypoxemic activity of alkylderivatives 5-(adamantane-1-yl)-4-R-1,2,4-triazole-3-thion. Zaporozhye medical journal, 2(89), 93–96 [in Ukrainian]. doi https://doi.org/10.14739/2310-1210.2015.2.42123.

Stefanov, А. V. (Ed) (2001) Мetodychni vkazivky po doklinichnomu vyvchenniu likarskykh zasobiv [Methodical instructions in preclinical studying of drugs]. Кyiv. [in Ukrainian].

Odyntsova, V. M., Kamyshnyi, O. M., & Polishchuk, N. М. (2017) Syntez, fizyko-khimichni vlastyvosti, protymikrobna ta protyhrybkova aktyvnist deiakykh 2-(2-((5-(adamantan-1-il)-4-R-1,2,4-triazol-3-il)tio)atsetyl)-N-R1-hidrazynokarbotioamidiv [Synthesis, physical-chemical properties, antimicrobial and antifungal activity of some 2-(2-((5-(adamantane-1-yl)-4-R-1,2,4-triazole-3-yl)thio)acetyl)-N-R1–hydrazine-carbothioamides]. Current issues in pharmacy and medicine: science and practice, 3(25), 264–272. [in Ukrainian]. doi: 10.14739/2409-2932.2017.3.112756.

Lapach, S. N., Chubenko, A. V., & Babich, P. N. (2001). Statisticheskie metody v mediko-biologicheskikh issledovaniyakh s ispol’zovaniem Excel [Statistical methods in biomedical research using Excel]. Kyiv: Morion. [in Russian].

Rebrova, O. Yu. (2002) Statisticheskij analiz medicinskikh dannykh. Primenenie paketa prikladnykh programm STATISTICA [Statistical analysis of medical data. Application of the STATISTICA software package]. Moscow: MediaSfera. [in Russian].

Downloads

How to Cite

1.
Odyntsova VM, Knysh Ye. G., YG, Panasenko OI. Synthesis, physical and chemical properties, antihypoxic activity of some 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl]-N-R1-1,3,4-thiadiazole-2-amines and 5-[((5-(adamantane-1-yl)-4-R-4H-1,2,4-triazole-3-yl)thio)methyl]-4-R1-4H-1,2,4-t. CIPM [Internet]. 2018Feb.16 [cited 2023Dec.9];(1). Available from: http://pharmed.zsmu.edu.ua/article/view/123590

Issue

No. 1 (2018)

Section

Synthesis of the biologically active compounds

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.     Лицензия Creative Commons
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)