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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, , 336 - 348, 20.05.2023
https://doi.org/10.33483/jfpau.1180794

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.

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]

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

Year 2023, , 336 - 348, 20.05.2023
https://doi.org/10.33483/jfpau.1180794

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.

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]
There are 22 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Research Article
Authors

Sergey Fedotov 0000-0002-0421-5303

Andrey Gotsulya 0000-0001-9696-221X

Yevhen Zaika 0000-0002-2152-233X

Tetyana Brytanova 0000-0003-1805-4552

Early Pub Date May 17, 2023
Publication Date May 20, 2023
Submission Date September 27, 2022
Acceptance Date January 11, 2023
Published in Issue Year 2023

Cite

APA Fedotov, S., Gotsulya, A., Zaika, Y., Brytanova, T. (2023). 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. Journal of Faculty of Pharmacy of Ankara University, 47(2), 336-348. https://doi.org/10.33483/jfpau.1180794
AMA Fedotov S, Gotsulya A, Zaika Y, Brytanova T. 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. Ankara Ecz. Fak. Derg. May 2023;47(2):336-348. doi:10.33483/jfpau.1180794
Chicago Fedotov, Sergey, Andrey Gotsulya, Yevhen Zaika, and Tetyana Brytanova. “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”. Journal of Faculty of Pharmacy of Ankara University 47, no. 2 (May 2023): 336-48. https://doi.org/10.33483/jfpau.1180794.
EndNote Fedotov S, Gotsulya A, Zaika Y, Brytanova T (May 1, 2023) 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. Journal of Faculty of Pharmacy of Ankara University 47 2 336–348.
IEEE S. Fedotov, A. Gotsulya, Y. Zaika, and T. Brytanova, “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”, Ankara Ecz. Fak. Derg., vol. 47, no. 2, pp. 336–348, 2023, doi: 10.33483/jfpau.1180794.
ISNAD Fedotov, Sergey et al. “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”. Journal of Faculty of Pharmacy of Ankara University 47/2 (May 2023), 336-348. https://doi.org/10.33483/jfpau.1180794.
JAMA Fedotov S, Gotsulya A, Zaika Y, Brytanova T. 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. Ankara Ecz. Fak. Derg. 2023;47:336–348.
MLA Fedotov, Sergey et al. “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”. Journal of Faculty of Pharmacy of Ankara University, vol. 47, no. 2, 2023, pp. 336-48, doi:10.33483/jfpau.1180794.
Vancouver Fedotov S, Gotsulya A, Zaika Y, Brytanova T. 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. Ankara Ecz. Fak. Derg. 2023;47(2):336-48.

Kapsam ve Amaç

Ankara Üniversitesi Eczacılık Fakültesi Dergisi, açık erişim, hakemli bir dergi olup Türkçe veya İngilizce olarak farmasötik bilimler alanındaki önemli gelişmeleri içeren orijinal araştırmalar, derlemeler ve kısa bildiriler için uluslararası bir yayım ortamıdır. Bilimsel toplantılarda sunulan bildiriler supleman özel sayısı olarak dergide yayımlanabilir. Ayrıca, tüm farmasötik alandaki gelecek ve önceki ulusal ve uluslararası bilimsel toplantılar ile sosyal aktiviteleri içerir.