Design, In Silico, and Experimental Evaluation of Novel Naproxen-Azetidinone Hybrids as Selective COX-2 Inhibitors.

ABSTRACT: The therapeutic use of non-steroidal anti-inflammatory drugs (NSAIDs) is limited by gastrointestinal and renal adverse effects caused by non-selective COX-1 and COX-2 inhibition. To address this issue, a new series of naproxen-azetidinone hybrids was rationally designed and synthesized to enhance COX-2 selectivity and reduce off-target toxicity. The synthesis involved esterification, hydrazide formation, Schiff base condensation, and intramolecular cyclization with chloroacetyl chloride. Structural characterization was achieved through FT-IR, ¹H NMR, and ¹³C NMR analyses. In silico ADMET profiling confirmed compliance with Lipinski's rule and predicted favorable gastrointestinal absorption. Molecular docking revealed high COX-2 binding affinities (-11.93 to -9.72 kcal

SUBMITTER: Khan AK 

PROVIDER: S-EPMC12654640 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature