Synthesis, characterization, and molecular docking study of 1,3-thiazinan-4-one synthesized via the reaction of 3- mercaptopropanoic acid with Schiff's base
DOI:
https://doi.org/10.31185/bsj.Vol21.Iss38.1516Keywords:
1,3-Thiazinan -4-one, Imine, Schiff's Bases, 3- Mercaptopropanoic Acid, Molecular DockingAbstract
Four compounds with heterocyclic six-membered rings (K1-K4) were synthesized in this work via the use of Schiff's bases and the appropriate reagents. To prepare Schiff bases, 4-chloroaniline was condensed with different aromatic aldehydes in absolute ethanol with a few drops of glacial acetic acid as a catalyst. The substituted 1,3-thiazinan-4-one was obtained by treating these Schiff bases with 3-mercaptopropanoic acid in anhydrous benzene under reflux conditions. The products were isolated, purified, and characterized by FT-IR, 1H- NMR spectroscopy, mass spectrometry, and C.H.N. analysis. Finally, molecular docking was used to investigate the inhibitory effects of the produced compounds (K1-K4) on the activity of acetylcholinesterase (AChE). All the 1,3-thiazinan-4-one derivatives showed enzyme inhibitory activity. The derivative K1, with a docking score of -9.3 kcal/mole, revealed good inhibitory effects on AChE inhibition compared with galanthamine, which was used as a reference drug.
References
1. Adriana, G.A. Berwaldt, C.T. Avila, T.B. Goulart, B.C. Moreira, T.P. Ferreira, P. Soares, N.S. Pedra, L. Spohr, Anita, R.M. Spanevello, W. Cunico, Synthesis of thiazolidin-4-ones and thiazinan-4-ones from 1-(2-aminoethyl)pyrrolidine as acetylcholinesterase inhibitors, Journal of Enzyme Inhibition and Medicinal Chemistry. 35 (2019) 31–41. https://doi.org/10.1080/14756366.2019.1680659.
2. Alshammari N.A.H., D.A. Bakhotmah, Synthesis, reactivity, antimicrobial, and anti-biofilm evaluation of fluorinated 4-amino-3-mercapto-1,2,4-triazin-5(4H)-one and their derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements. 198 (2022) 385–396. https://doi.org/10.1080/10426507.2022.2150856.
3. Biovia D.S., Discovery studio modeling environment, Dassault Syst`emes,San Diego, Calif (2013) software.
4. Chen Z.-R., J.-B. Huang, S.-L. Yang, F.-F. Hong, Role of Cholinergic Signaling in Alzheimer’s Disease, Molecules. 27 (2022) 1816. https://doi.org/10.3390/molecules27061816.
5. Halder N., G. Lal, Cholinergic System and Its Therapeutic Importance in Inflammation and Autoimmunity, Frontiers in Immunology. 12 (2021) 660342. https://doi.org/10.3389/fimmu.2021.660342.
6. Ibrahim A.M., M.E. Shoman, Mohamed, A.M. Hayallah, Gamal El-Din A. Abuo-Rahma, Chemistry and Applications of Functionalized 2,4‐Thiazolidinediones, European Journal of Organic Chemistry (Online). 26 (2023). https://doi.org/10.1002/ejoc.202300184.
7. Juan David Villeda‐González, José Luis Gómez‐Olivares, Luis Arturo Baiza‐Gutman, New paradigms in the study of the cholinergic system and metabolic diseases: Acetyl‐and‐butyrylcholinesterase, Journal of Cellular Physiology. (2024). https://doi.org/10.1002/jcp.31274.
8. Kabir E., M. Uzzaman, A review on biological and medicinal impact of heterocyclic compounds, Results in Chemistry. 4 (2022) 100606. https://doi.org/10.1016/j.rechem.2022.100606.
9. Kadhim M.A., M.G. Mukhlif, E.W. Gayadh, Emad K.M. Zangana, M.A. Mohaisen, M.M. Matar, S.A. Rizk, Synthesis, design, biological activity, DFT study and molecular docking of new 1,2,4-triazine and 1,2,4-triazol derivatives bearing the phthalazine moiety, Journal of Molecular Structure. (2024) 140384–140384. https://doi.org/10.1016/j.molstruc.2024.140384.
10. Lin S., L. Xiang, C. Liu, X. Chen, Y. Ye, Recent progress in cycloaddition reactions of cyclopropenone, Arabian Journal of Chemistry. 17 (2024) 105845–105845. https://doi.org/10.1016/j.arabjc.2024.105845.
11. Mohamed A.H., S.M. Mostafa, A.A. Aly, A.A. Hassan, E.M. Osman, A.A. Nayl, A.B. Brown, Elshimaa M. N. Abdelhafez, Novel quinoline/thiazinan-4-one hybrids; design, synthesis, and molecular docking studies as potential anti-bacterial candidates against MRSA, RSC Advances. 13 (2023) 14631–14640. https://doi.org/10.1039/d3ra01721d.
12. Mukhlif M.G., O.J. Mahdi, A.K. Alywee, Formation of new substituted (1,3)oxazepine 1,5-diones via reaction of Exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic Anhydride with Schiff’s bases, AIP Conference Proceedings. (2023). https://doi.org/10.1063/5.0118487.
13. Mukhlif M.G., O.J. Mahdi, M.J. Bichan, Synthesis, Characterization, Molecular Docking, and Computational Study of novel Spirothiazolidinone Compounds, Journal of Molecular Structure. (2025) 141517–141517. https://doi.org/10.1016/j.molstruc.2025.141517.
14. Nimgampalle M., H. Chakravarthy, S. Sharma, S. Shree, A.R. Bhat, J.A. Pradeepkiran, V. Devanathan, Neurotransmitter systems in the etiology of major neurological disorders: Emerging insights and therapeutic implications, Aging Research Reviews. 89 (2023) 101994–101994. https://doi.org/10.1016/j.arr.2023.101994.
15. Pal R., Ghanshyam Teli, G. Swamy, Prasad Sanjay Dhiwar, Designing strategies, structural activity relationship and biological activity of recently developed nitrogen containing heterocyclic compounds as epidermal growth factor receptor tyrosinase inhibitors, Journal of Molecular Structure. 1291 (2023) 136021–136021. https://doi.org/10.1016/j.molstruc.2023.136021.
16. Permana A., A.W.R. Akili, A. Hardianto, J. Latip, A. Sulaeman, T. Herlina, Virtual Screening, Toxicity Evaluation and Pharmacokinetics of Erythrina Alkaloids as Acetylcholinesterase Inhibitor Candidates from Natural Products, Advances and Applications in Bioinformatics and Chemistry. Volume 17 (2025) 179–201. https://doi.org/10.2147/aabc.s495947.
17. Qadir T., A. Amin, P.K. Sharma, I. Jeelani, H. Abe, A Review on Medicinally Important Heterocyclic Compounds, The Open Medicinal Chemistry Journal. 16 (2022). https://doi.org/10.2174/18741045-v16-e2202280.
18. Rajagopalan V., S. Venkataraman, D.S. Rajendran, V. Vinoth Kumar, V.V. Kumar, G. Rangasamy, Acetylcholinesterase biosensors for electrochemical detection of neurotoxic pesticides and acetylcholine neurotransmitter: A literature review, Environmental Research. 227 (2023) 115724. https://doi.org/10.1016/j.envres.2023.115724.
19. Tajdari M., A. Peyrovinasab, M. Bayanati, M. Ismail Mahboubi Rabbani, A.H. Abdolghaffari, A. Zarghi, Dual COX-2/TNF-α Inhibitors as Promising Anti-inflammatory and Cancer Chemopreventive Agents: A Review, Iranian Journal of Pharmaceutical Research. 23 (2024). https://doi.org/10.5812/ijpr-151312.
20. Taylor C.J., A. Pomberger, K.C. Felton, R. Grainger, M. Barecka, T.W. Chamberlain, R.A. Bourne, C.N. Johnson, A.A. Lapkin, A Brief Introduction to Chemical Reaction Optimization, Chemical Reviews. 123 (2023). https://doi.org/10.1021/acs.chemrev.2c00798.
21. Teleanu R.I., Neurotransmitters—Key factors in neurological and neurodegenerative disorders of the central nervous system, International Journal of Molecular Sciences. 23 (2022) 1–24. https://doi.org/10.3390/ijms23115954.
22. Trott O., A.J. Olson, AutoDockVina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, J. Comput. Chem. 31 (2) (2010) 455–461, https://doi.org/10.1002/jcc.21334.
23. Wojtunik-Kulesza K., M. Rudkowska, K. Kasprzak-Drozd, A. Oniszczuk, K. Borowicz-Reutt, Activity of Selected Group of Monoterpenes in Alzheimer’s Disease Symptoms in Experimental Model Studies—A Non-Systematic Review, International Journal of Molecular Sciences. 22 (2021) 7366. https://doi.org/10.3390/ijms22147366.
24. Xing S., Q. Li, B. Xiong, Y. Chen, F. Feng, W. Liu, H. Sun, Structure and therapeutic uses of butyrylcholinesterase: Application in detoxification, Alzheimer’s disease, and fat metabolism, Medicinal Research Reviews. 41 (2020) 858–901. https://doi.org/10.1002/med.21745.
25. Zhang K., A.B. Aslan, AI technologies for education: Recent research & future directions, Computers and Education: Artificial Intelligence. 2 (2021) 100025. https://doi.org/10.1016/j.caeai.2021.100025
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