Design, Molecular Docking, and Pharmacokinetic Evaluation of Naproxen-Based 2‑Azetidinone Derivatives for Cancer Treatment
DOI:
https://doi.org/10.32947/ajps.v26i1.1344Keywords:
EGFR inhibitor, Osimertinib , ADME analysis, Naproxen derivative, Molecular DockingAbstract
This study investigates the design, molecular docking, and ADME properties of six novel naproxen derivatives featuring a 2-azetidinone ring, targeting EGFR kinase. Molecular docking was conducted using the crystal structure of the EGFR mutant complexed with Osimertinib (PDB ID: 6LUD). The derivatives were compared with Osimertinib using GOLD software to evaluate binding affinity and fitness.
Results showed that several compounds exhibited stronger predicted binding interactions within the EGFR active site, with NR1 and NR2 displaying notably high PLP fitness scores (75.14 and 73.90, respectively). ADME analysis via SwissADME confirmed that all compounds complied with Lipinski’s Rule of Five and exhibited favorable pharmacokinetic properties, including high gastrointestinal absorption and drug-likeness, which supports their potential for oral bioavailability. These computational findings suggest that the derivatives may serve as promising candidates for EGFR inhibition; however, experimental studies are required to validate their biological efficacy and therapeutic potential against mutation-mediated resistance. Overall, the results underscore the potential of 2-azetidinone-based naproxen derivatives as pharmacokinetically viable EGFR inhibitors, warranting further cellular and in vivo evaluation.References
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