DESIGN, SYNTHESIS AND MOLECULAR DOCKING OF SOME DERIVATIVES OF 9-METHYLPYRAZOLO[1,5-d][1,2,4]TRIAZOLO [3,4-f][1,2,4]TRIAZINE-3-THIOL

Year 2023, Volume: 47 Issue: 2, 336 - 348, 20.05.2023

Sergey Fedotov , Andrey Gotsulya , Yevhen Zaika , Tetyana Brytanova

https://doi.org/10.33483/jfpau.1180794

Cited By: 2

Abstract

Objective: The purpose of the work was to elaboration effective techniques for the synthesis of advanced condensed heterocyclic systems based on pyrazole and 1,2,4-triazole. In the process of realizing the set goal, a number of new pyrazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazines have been synthesized.
Material and Method: Identity of synthesized compounds has been confirmed by elemental analysis, 1H-NMR, LC-MS techniques. The pharmacological potential of the obtained substances has been determined by molecular docking method.

Result and Discussion: The optimal conditions for the preparation of pyrazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazines has been determined. Based on the results of molecular docking, a row of substances with high potential for anti-inflammatory and antifungal activity has been identified. In silico studies were carried out using the models of cyclooxygenase-2, lanosta-8,24-dien-3β-ol 14α-demethylase, anaplastic lymphoma kinase.

Keywords

1,2-diazole, 1,2,4-triazole, chemistry, molecular docking, transformation

BAZI 9-METİLPİRAZOLO[1,5-d][1,2,4]TRİAZOLO[3,4-f][1,2,4]TRİAZİN-3-TİYOL TÜREVLERİNİN TASARIMI, SENTEZİ VE MOLEKÜLER YERLEŞTİRİLMESİ

Abstract

Amaç: Çalışmanın amacı, pirazol ve 1,2,4-triazole dayalı gelecek vaat eden kondanse heterosiklik sistemlerin sentezi için etkili yöntemler geliştirmektir. Belirlenen hedefi gerçekleştirme sürecinde, bir dizi yeni pirazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazin sentezlenmiştir.
Gereç ve Yöntem: Sentezlenen bileşiklerin yapısı, element analizi, 1H-NMR, LC-MS teknikleri ile doğrulanmıştır. Elde edilen maddelerin farmakolojik potansiyeli moleküler modelleme yöntemi ile belirlenmiştir.

Sonuç ve Tartışma: Pirazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazinlerin hazırlanması için optimal koşullar belirlendi. Moleküler yerleştirme sonuçlarına dayanarak, anti-inflamatuar ve antifungal aktivite için yüksek potansiyele sahip bir dizi madde tanımlanmıştır. Siklooksijenaz-2, lanosta-8,24-dien-3β-ol 14α-demetilaz, anaplastik lenfoma kinazlarının modelleri kullanılarak in siliko çalışmalar yürütülmüştür.

Keywords

1,2-diazol, 1,2,4-triazol, dönüşüm, kimya, moleküler yerleştirme

References

• 1. Boraei, A.T.A., Sarhan, A.A.M., Yousuf, S., Barakat, A. (2020). Synthesis of a new series of nitrogen/sulfur Heterocycles by linking four rings: Indole; 1,2,4-triazole; pyridazine; and quinoxaline. Molecules, 25(3), 450. [CrossRef]
• 2. Shcherbyna, R., Panasenko, O., Polonets, O., Nedorezanıuk, N., Duchenko, M. (2021). Synthesis, antimicrobial and antifungal activity of ylidenhydrazides of 2-((4-R-5-R1-4Н-1,2,4-triazol-3-yl)thio)acetaldehydes. Journal of Faculty of Pharmacy of Ankara University, 45(3), 504-514. [CrossRef]
• 3. Frolova, Y., Kaplaushenko, A., Nagornaya, N. (2020). Design, synthesis, antimicrobial and antifungal activities of new 1,2,4-triazole derivatives containing 1H-tetrazole moiety. Journal of Faculty of Pharmacy of Ankara University, 44(1), 70-88. [CrossRef]
• 4. Samelyuk, Y.G., Kaplaushenko, A.G. (2014). Synthesis of 3-alkylthio(sulfo)-1,2,4-triazoles, containing methoxyphenyl substituents at C5atoms, their antipyretic activity, propensity to adsorption and acute toxicity. Journal of Chemical and Pharmaceutical Research, 6(5), 1117-1121.
• 5. Aggarwal, R., Sumran, G. (2020). An insight on medicinal attributes of 1,2,4-triazoles. European Journal of Medicinal Chemistry, 205, 112652. [CrossRef]
• 6. Zaher, N.H., Mostafa, M.I., Altaher, A.Y. (2020). Design, synthesis and molecular docking of novel triazole derivatives as potential CoV helicase inhibitors. Acta Pharmaceutica, 70(2), 145-159. [CrossRef]
• 7. Vanjare, B.D., Mahajan, P.G., Dige, N.C., Raza, H., Hassan, M., Han, Y., Lee, K.H. (2020). Novel 1,2,4-triazole analogues as mushroom tyrosinase inhibitors: synthesis, kinetic mechanism, cytotoxicity and computational studies. Molecular Diversity, 25, 2089-2106 [CrossRef]
• 8. Safonov, A. (2020). Method of synthesis novel N'-substituted 2-((5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-3-yl)thio)acetohydrazides. Journal of Faculty of Pharmacy of Ankara University, 44(2), 242-252. [CrossRef]
• 9. Safonov, A., Nevmyvaka, A., Panasenko, O., Knysh, Y. (2021). Microwave synthesis of 3- and 4-substituted-5-((3-phenylpropyl)thio)-4H-1,2,4-triazoles. Journal of Faculty of Pharmacy of Ankara University, 45(3), 457-466. [CrossRef]
• 10. Simurova, N.V., Maiboroda, O.I. (2021) Antiviral activity of 1,2,4-triazole derivatives (microreview). Chemistry of Heterocyclic Compounds, 57, 420-422. [CrossRef]
• 11. Singla, N. (2020). Synthetic and medicinal attributes of 1,2,4-triazole derivatives, Annals of Tropical Medicine & Public Health, 23(14), SP231541.
• 12. Hotsulia, A.S., Fedotov, S.O. (2019). Synthesis, structure and properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides. Current Issues in Pharmacy and Medicine: Science and Practice, 12(1), 4-9. [CrossRef]
• 13. Fedotov, S.O., Hotsulia, A.S. (2021). Synthesis and properties of S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol. Current Issues in Pharmacy and Medicine: Science and Practice, 14(3), 268-274. [CrossRef]
• 14. Karrouchi, K., Chemlal, L., Taoufik, J., Cherrah, Y., Radi, S., El Abbes Faouzi, M., Ansar, M. (2016). Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety. Annales Pharmaceutiques Françaises, 74(6), 431-438.
• 15. Varynskyi, B., Kaplaushenko, A., Parchenko, V. (2018). Electrospray ionization mass spectrometry fragmentation pathways of salts of some 1,2,4-triazolylthioacetate acids, the active pharmaceutical ingredients. The Asian Journal of Pharmaceutical and Cinical Research, 10, 303-312. [CrossRef]
• 16. Karpun, Y.O., Karpenko, Y.V., Parchenko, M.V., Bihdan, O.A. (2020). Molecular docking and bioavailability of S-alkylderivatives 5-(3-fluorophenyl)-, 5-(5-bromofuran-2-yl)- and -(((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl))thio)methyl)-4-methyl-4H-1,2,4-triazole in silico methods. Current Issues in Pharmacy and Medicine: Science and Practice, 13(1), 38-45. [CrossRef]
• 17. El Bakri, Y., Marmouzi, I., El Jemli, M., Anouar, E.H., Karthikeyan, S., Harmaoui, A., Faouzi, M.E.A., Mague, J.T., Essassi, E.M. (2019). Synthesis, biological activity and molecular modeling of a new series of condensed 1,2,4-triazoles. Bioorganic Chemistry, 92, 103193. [CrossRef]
• 18. Protein Data Bank, pdb.http://www.rcsb.org/pdb/home/home.do
• 19. MarvinSketch version 17.21.0, ChemAxon Retrieved from https://chemaxon.com/
• 20. Trott O., Olson A.J. (2020). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 31, 455-461.
• 21. Ghanaat, J., Khalilzadeh, M.A., Zareyee, D. (2020). Molecular docking studies, biological evaluation and synthesis of novel 3-mercapto-1,2,4-triazole derivatives. Molecular Diversity, 25(1), 223-232. [CrossRef]
• 22. El-Reedy, A.A.M., Soliman, N.K. (2020). Synthesis, biological activity and molecular modeling study of novel 1,2,4-triazolo[4,3-b][1,2,4,5]tetrazines and 1,2,4-triazolo[4,3-b][1,2,4]triazines. Scientific Reports, 10, 6137. [CrossRef]