In-silico molecular docking, ADME study of new azetidin-2-one derivatives having imidazole moiety targeting cyclooxygenase-2 Enzyme
DOI:
https://doi.org/10.32947/ajps.v25i5.1313Keywords:
Azetidin-2-one, cyclooxygenase-2 inhibitors, imidazole, ADME, anti-inflammatoryAbstract
Background: Non-steroidal anti-inflammatory drugs re commonly used medications as anti-inflammatory, analgesic and antipyretic agents. However, they have many limitations due to the adverse effect, such as gastric irritation and gastric ulceration. Recently, β-lactams have been approved as chosen scaffolds due to their wide range of biological characteristics.
Objective: goal of this research was the development of a series of new azetidin-2-one derivatives (B1-6) and assessment of their function as cox-2 inhibitory agents.
Methods: crystal structure diclofenac complexed with active site of cyclooxygenase-2 from protein data bank, then docked with our new azetidine-2-one derivatives.
Results: molecular docking protocol results proposed that these azetidine-2-one derivatives have sufficiently strong binding interactions within active site of COX-II. they have PLP fitness scores ranges between 66-74 respectively, whereas the fitness score of the standard drug (diclofenac) was (69). Additionally, newly designed ligands show good Swiss-ADME variables, revealing that they might be compounds with good bioavailability when taken orally.
Conclusion: Three ligands exhibit superior PLP fitness compared to the reference ligand, while one demonstrates a comparable score at the active site of COX-II. This suggests that the new derivatives yield encouraging outcomes and may serve as modeling substances for the development of new anti-inflammatory drugs. Nevertheless, more pharmacological assessment is required.
References
1- Monther F. M., Ashour D. & Ali M. H.. Synthesis and Characterization of New Ligands attached to NSAIDs Moiety. International Journal of Advanced Research. 2015, 3(6), 172-192.
2- Tayanny M. M.,
João J. M. R., Marcus T. S., Ines R. V., Tais F. G., Renal effects of selective cyclooxygenase-2 inhibitor anti-inflammatory drugs: A systematic review and meta-analysis. Exploratory Research in Clinical and Social Pharmacy. 2024, 15. https://doi.org/10.1016/j.rcsop.2024.100475.
3- Sarmad A. F., Karima F. A., Wesen A. M. In-SilicoEvaluation of Binding Interaction and ADME Properties of Novel Pyrazoline and Pyrimidine Derivatives Targeting Cyclooxygenase-2 Enzyme. Al Mustansiriyah Journal of Pharmaceutical Sciences. 2025. 25(1), 110-130. https://doi.org/10.32947/ajps.v25i1.1148
4- Monther F.M., Ashour H. D., Ahmed K. H. Design, Synthesis and Preliminary Pharmacological Evaluation of Mutual Prodrug of Non-Steroidal Anti-Inflammatory Drugs Coupling With Natural Anti-Oxidants Via Glycine. Iraqi Journal of Pharmaceutical Sciences (IJPS). 2013. Vol. 13(1). 155-169. https://doi.org/10.32947/ajps.v13i1.211
5- Muheyuddeen G, Khan M, Sahu N. Design, synthesis, and biological evaluation of novel imidazole derivatives as analgesic and anti-inflammatory agents: experimental and molecular docking insights. Scientific Reports. 2024. 14(1), 1-14. http://dx.doi.org/10.1038/s41598-024-72399-8
6- Yerigeri M, Murari S, Vishwanath B. Anti-Tubercular and Anti-Inflammatory Activities of Azetidin-2-One Derivatives and Their Effects on the Activity of Phospholipase A2. Current Drug Targets. 2008 4(2), 190-193. https://doi.org/10.2174/157340608783789149
7- Staudinger, H. . Zur Kenntniss der Ketene. Diphenylketen. Justus Liebigs Annalen der Chemie. 1907. 356, 51–123.
8- Kumar Gupta S, Mishra A. Synthesis, Characterization & Screening for Anti-Inflammatory & Analgesic Activity of Quinoline Derivatives Bearing Azetidinones Scaffolds. Anti-inflammatory & anti-allergy agents in medicinal chemistry. 2016. 15(1), 31-43. https://doi.org/10.2174/1871523015666160210124545
9- Drăgan m, daniela stan c, profire l. Assessment of in vitro antioxidant and anti-inflammatory activities of new azetidin-2-one derivatives of ferulic acid. Farmacia. 2016. 64(5), 717-721.
10- Utkarsha N., Vandana G. In vitro cytotoxic effects, in silico studies, some metabolic enzymes inhibition, and vibrational spectral analysis of novel β-amino alcohol compounds. Frontiers in drug discovery. 2024. 4, 1362456. https://doi.org/10.3389/fddsv.2024.1362456
11- Ugurlu A., A comprehensive overview of in silico strategies in modern drug discovery. Computational Chemistry Reviews. 2024. 10. 45-68. https://doi.org/10.1016/j.ccr.2024.01.005
12- Khalilov A, Tüzün B, Cakmak N. Cytotoxic effect, spectroscopy, DFT, enzyme inhibition, and moleculer docking studies of some novel mesitylaminopropanols: Antidiabetic and anticholinergics and anticancer potentials. Journal of Molecular Liquids. 2021. 344, 117761. https://doi.org/10.1016/j.molliq.2021.117761
13- Prasanna S, Doerksen R. Topological Polar Surface Area: A Useful Descriptor in 2D-QSAR. Current medicinal chemistry. 2009 16(1), 21. https://doi.org/10.2174/092986709787002817
14- Palm K, Stenberg P, Artursson P. Polar molecular surface properties predict the intestinal absorption of drugs in humans. Pharmaceutical research. 1997. 14(5), 568-571. https://doi.org/10.1023/a:1012188625088
15- Leslie Z. Benet, Chelsea M. Hosey, Tudor I. Oprea. BDDCS, the Rule of 5 and drugability. Advanced Drug Delivery Reviews. 2016. 101, 89-98. https://doi.org/10.1016/j.addr.2016.05.007
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