Prediction of the Antiinflammatory Activity of New S-alkyl Derivatives of 1,2,4-triazol-3-thiones Using the PASS Computer Program and Molecular Docking

Natalya Mykolaivna Chalenko (1) , Anna Olegovna Syrovaya (2) , Natalya P Kobzar (3) , Maryna V Rakhimova (4) , Irina A Sych (5) , Igor Vladimirovich Sych (6)
(1) Kharkiv National Medical University , Ukraine
(2) Kharkiv National Medical University , Ukraine
(3) National University of Pharmacy , Ukraine
(4) National University of Pharmacy , Ukraine
(5) National University of Pharmacy , Ukraine
(6) Hon. Prof. M. S. Bokarius Kharkiv Research Institute of Forensic Examinations , Ukraine


The strategy of rational approaches to the search for selective COX-2 inhibitors as potential antiinflammatory agents has been proposed and elaborated. It is based on the use of PASS-prediction and molecular docking. The choice of the basic structure of 4-amino-3-thio-1,2,4-triazole as a promising object of chemical modification has been substantiated. Using a modification of the primary molecule, a virtual library of S-derivatives of 5-substituted 4-amino(pyrrol)3-thio-4H-1,2,4-triazoles in the amount of 100 compounds (ten groups) has been obtained by introducing various pharmacophore fragments. Based on the analysis of the results of the PASS-prediction and molecular docking, six of the ten planned groups of compounds have been selected for the synthesis as promising selective COX-2 inhibitors. The reliability of the prediction results has already been confirmed for one of the promising group 4-amino-5-(pyridine-4-yl)-1,2,4-triazole (4Н)-3-yl-thioacetamides.

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Assyl, B., Georgiyants, V.A., & Perekhoda, L.O. (2014). Study of acyl substitution on docking properties of substituted dihydrogercetines as anti-inflammatory agents. Journal of Chemical and Pharmaceutical Research, 6(4), 749-753.
Cai, H., Huang, X., Xu, S., Shen, H., Zhang, P., Huang, Y., Jiang, J., Sun, Y., Jiang, B., Wu, X., Yao, H., & Xu, J. (2016). Discovery of novel hybrids of diaryl-1,2,4-triazoles and caffeic acid as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase for cancer therapy. European Journal of Medicinal Chemistry, 108, 89-103. doi: 10.1016/j.ejmech.2015.11.013
Chalenko, N.M., Demchenko, A.M., & Syrovaya, G.O. (2019). Synthesis and biological activity of 4-amino-5-(pyridin-4-yl)-1,2,4-triazole(4H)-3-il-thioacetamides. Actual problems of experimental and clinical biochemistry: materials of the international scientific-practical conference (p. 79). Kharkiv, Ukraine: Kharkiv National Medical University.
Chalenko, N.M. & Syrovaya, G.O. (2017). The feasibility of using the prediction of activity spectra for substances program for targeted synthesis of potential non-steroidal class 3-thio-1,2,4-triazoles. Bioethics and Biosafety: Multidisciplinary Aspects: Materials of a Scientific and Practical Conference with International Participation dedicated to the 105th Anniversary of V.K. Viskovich (pp. 160-161). Kharkiv, Ukraine: Kharkiv National Medical University.
Cordero, J.A., Camacho, M., Obach, R., Domenech, J., & Vila, L. (2001). In vitro based index of topical anti-inflammatory activity to compare a series of NSAIDs. European Journal of Pharmaceutics and Biopharmaceutics, 51(2), 135-142. doi: 10.1016/s0939-6411(00)00149-1
Jiang, B., Zeng, Y., Li, M.J., Xu, J.Y., Zhang, Y.N., Wang, Q.J., Sun, N.Y., Lu, T., & Wu, X.M. (2010). Design, synthesis, and biological evaluation of 1,5-diaryl-1,2,4-triazole derivatives as selective cyclooxygenase-2 inhibitors. Archiv der Pharmazie, 343(9), 500-508. doi: 10.1002/ardp.200900227
Jin, J.Y., Zhang, L.X., Zhang, A.J., Lei, X.X., & Zhu, J.H. (2007). Synthesis and Biological Activity of Some Novel Derivatives of 4-Amino-3-(D-galactopentitol-1-yl)-5-mercapto-1,2,4-triazole. Molecules, 12(8), 1596-1605. doi: 10.3390/12081596
Khanage, S.G., Raju, S.A., Mohite, P.B., & Pandhare, R.B. (2012). Synthesis and Pharmacological Evaluation of Some New Pyrimidine Derivatives Containing 1,2,4-Triazole. Advanced Pharmaceutical Bulletin, 2(2), 213-222. doi: 10.5681/apb.2012.033
Kurumbail, R.G., Stevens, A.M., Gierse, J.K., McDonald, J.J., Stegeman, R.A., Pak, J.Y., Gildehaus, D., Miyashiro, J.M., Penning, T.D., Seibert, K., Isakson, P.C., & Stallings, W.C. (1997). Correction: Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature, 385, 555. doi: 10.1038/385555b0
Lagunin, A., Stepanchikova, A., Filimonov, D., & Poroikov, V. (2000). PASS: prediction of activity spectra for biologically active substances. Bioinformatics, 16(8), 747-748. doi: 10.1093/bioinformatics/16.8.747
Laube, M., Kniess, T., & Pietzsch, J. (2016). Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy—A Hypothesis-Driven Review. Antioxidants, 5(2), 14. doi: 10.3390/antiox5020014
Leelananda, S.P. & Lindert, S. (2016). Computational methods in drug discovery. Beilstein Journal of Organic Chemistry, 12, 2694-2718. doi: 10.3762/bjoc.12.267
Mioc, M., Soica, C., Bercean, V., Avram, S., Balan-Porcarasu, M., Coricovac, D., Ghiulai, R., Muntean, D., Andrica, F., Dehelean, C., Spandidos, D.A., Tsatsakis, A.M., & Kurunczi, L. (2017). Design, synthesis and pharmaco-toxicological assessment of 5-mercapto-1,2,4-triazole derivatives with antibacterial and antiproliferative activity. International Journal of Oncology, 50(4), 1175-1183. doi: 10.3892/ijo.2017.3912
Moise, M., Sunel, V., Profire, L., Popa, M., Desbrieres, J., & Peptu, C. (2009). Synthesis and Biological Activity of Some New 1,3,4-Thiadiazole and 1,2,4-Triazole Compounds Containing a Phenylalanine Moiety. Molecules, 14(7), 2621-2631. doi: 10.3390/molecules14072621
Mozziconacci, J.C., Arnoult, E., Bernard, P., Do, Q.T., Marot, C., & Morin-Allory, L. (2005). Optimization and validation of a docking-scoring protocol; application to virtual screening for COX-2 inhibitors. Journal of Medicinal Chemistry, 48(4), 1055-1068. doi: 10.1021/jm049332v
Oliveira, J.W.F., Rocha, H.A.O., de Medeiros, W.M.T.Q., & Silva, M.S. (2019). Application of Dithiocarbamates as Potential New Antitrypanosomatids-Drugs: Approach Chemistry, Functional and Biological. Molecules, 24(15), 2806. doi: 10.3390/molecules24152806
Parasuraman, S. (2011). Prediction of activity spectra for substances. Journal of Pharmacology and Pharmacotherapeutics, 2(1), 52-53. doi: 10.4103/0976-500X.77119
Sliwoski, G., Kothiwale, S., Meiler, J., & Lowe Jr., E.W. (2014). Computational Methods in Drug Discovery. Pharmacological Reviews, 66(1), 334-395. doi: 10.1124/pr.112.007336
Sondhi, S.M., Dinodia, M., Singh, J., & Rani, R. (2007). Heterocyclic Compounds as Anti-Inflammatory Agents. Current Bioactive Compounds, 3(2), 91-108. doi: 10.2174/157340707780809554
Torres, P.H.M., Sodero, A.C.R., Jofily, P., & Silva Jr., F.P. (2019). Key Topics in Molecular Docking for Drug Design. International Journal of Molecular Sciences, 20(18), 4574. doi: 10.3390/ijms20184574
Zhuang, C., Zhang, W., Sheng, C., Zhang, W., Xing, C., & Miao, Z. (2017). Chalcone: A Privileged Structure in Medicinal Chemistry. Chemical Reviews, 117(12), 7762-7810. doi: 10.1021/acs.chemrev.7b00020


Natalya Mykolaivna Chalenko
Anna Olegovna Syrovaya
Natalya P Kobzar
Maryna V Rakhimova
Irina A Sych
Igor Vladimirovich Sych (Primary Contact)
Chalenko NM, Syrovaya AO, Kobzar NP, Rakhimova MV, Sych IA, Sych IV. Prediction of the Antiinflammatory Activity of New S-alkyl Derivatives of 1,2,4-triazol-3-thiones Using the PASS Computer Program and Molecular Docking. Borneo J Pharm [Internet]. 2020Feb.27 [cited 2024Jul.18];3(1):36-43. Available from:

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