Abstract
Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer, atherosclerosis, Alzheimer's disease, and Parkinson`s disease. Potential cardiovascular and hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based on the structure of previously investigated newly synthesized β-hydroxy-β-arylpropanoic acids, two groups of compounds were designed: analogs in which one of the benzene rings was replaced by a pyrazole, while the carboxyl group was retained, and amides of β-hydroxy-β-arylpropanoic acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding energies than the designed acids, which makes them attractive target compounds for synthesis and further examination.
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References
1. Ahmed AU. An overview of inflammation: mechanism and consequences. Front Biol. 2011;6(4):274-81.
2. Tsalamandris S, Antonopoulos AS, Oikonomou E, Papamikroulis GA, Vogiatzi G, Papaioannou S, et al. The role of inflammation in diabetes: current concepts and future perspectives. Eur Cardiol. 2019;14(1):50-9.
3. Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating C, Joers V. Inflammation and immune dysfunction in Parkinson`s disease. Nat Rev Immunol. 2022;22(11): 657-73.
4. Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer's disease. Alzheimers Dement: Transl Res Clin Interv. 2018;4:575-90.
5. Moriya J. Critical roles of inflammation in atherosclerosis. J Cardiol. 2019;73(1):22-7.
6. Zhao H, Wu L, Yan G. Chen Y, Zhou M, Wu Y, et al. Inflammation and tumor progression: signaling pathways and targeted intervention. Sig Transduct Target Ther. 2021;6:263-309.
7. Deshmukh SK, Srivastava SK, Poosarla T, Dyess DL, Holliday NP, Singh AP, et al. Inflammation, immunosuppressive microenvironment and breast cancer: opportunities for cancer prevention and therapy. Ann Transl Med. 2019;7(20):593-607.
8. Lim B, Woodward WA, Wang X, Reuben JM, Ueno NT. Inflammatory breast cancer biology: the tumour microenvironment is key. Nat Rev Cancer. 2018; 18(8):485-99.
9. Janakiram NB, Rao CV. The role of inflammation in colon cancer. Adv Exp Med Biol. 2014;816:25-52.
10. Wang D, DuBois RN. The role of anti-inflammatory drugs in colorectal cancer. Annu Rev Med. 2013;14(64):131-44.
11. Vane JR, Bakhle YS, Botting RM. Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 1998;38(1):97-120.
12. Roche VF, Williams DA, Lemke TL, Zito SW. Foye's Principles of Medicinal Chemistry. 8th ed. Philadelphia: Lippincott Williams & Wilkins; 2019.
13. Capone ML, Tacconelli S, Sciulli MG, Patrignani P. Clinical pharmacology of selective COX-2 inhibitors. Int J Immunopathol Pharmacol. 2003;16(2 Suppl):49-58.
14. Guedes IA, de Magalhães CS, Dardenne LE. Receptor–ligand molecular docking. Biophys Rev. 2014;6:75-87.
15. Jakhar R, Dangi M, Khichi A, Chhillar AK. Relevance of molecular docking studies in drug designing. Curr Bioinform. 2020;15(4):270-8.
16. Ferreira LG, Santos dos RN, Oliva G, Andricopulo A. Molecular docking and structure-based drug design strategies. Molecules. 2015;20:13384-421.
17. Savić J, Dilber S, Marković B, Milenković M, Vladimirov S, Juranić I. Docking studies and α-substitution effects on the anti-inflammatory activity of β-hydroxy-β-arylpropanoic acids. Molecules. 2011;16(8):6645-55.
18. Savić J, Dilber S, Milenković M, Kotur-Stevuljević J, Marković B, Vladimirov S, Brborić J. Docking studies, synthesis and biological evaluation of β-aryl-β-hydroxy propanoic acids for anti-inflammatory activity. Med Chem. 2017;13(2): 186-96.
19. Eberhardt J, Santos-Martins D, Tillack AF. Forli S. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J Chem Inform Model. 2021;61(8):3891-8.
20. Trott O, Olson, AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comp Chem. 210;31(2):455-61.
21. The PyMOL Molecular Graphics System. Version 2.0. Schrödinger, LLC.
22. ChemOffice Version 7.0 ultra. Cambridge Soft Corporation, Software Publishers Association, 1730 M Street, NW, Suite 700, Washington D.C.20036 (2002), 452–1600 USA.
23. Brune K, Hinz B. Selective cyclooxygenase‐2 inhibitors: similarities and differences. Scand. J Rheumatol. 2004;33(1):1-6.
24. Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Gildehaus D et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996;384:644-48.
25. Correa CM, de Paula AF, da Silva GM, Sant'Anna CM, Fraga CA, Barreiro EJ. The molecular basis of COX-2 versus COX-1 selectivity of lumiracoxib by molecular docking studies. Lett Drug Des Discov. 2007;4(6):422-5.
26. Buvanendran A, Barkin R. Lumiracoxib. Drug Today. 2007;43(3):137-47.
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