In-silico molecular docking, ADME study of new azetidin-2-one derivatives having imidazole moiety targeting cyclooxygenase-2 Enzyme
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Abstract
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.
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