Investigation of 𝑁-(۵-nitrothiazol-۲-yl)-۲-((۴-oxo-۳,۴-Dihydroquinazolin-۲-yl) Thio) Acetamide Derivatives as Potential EGFR Kinase Inhibitors

Epidermal growth factor receptor (EGFR) inhibitors are essential in cancer therapy, as they specifically target hyperactive EGFR, a principal facilitator of tumor proliferation and viability in several malignancies. Hybrid molecules composed of thiazole and quinazolinone scaffolds have great potential as strong EGFR inhibitors because their therapeutic properties work well together. We designed N-(۵-nitrothiazol-۲-yl)-۲-((۴-oxo-۳,۴-dihydroquinazolin-۲-yl) thio) acetamide derivatives to explore the pharmacophoric features of these scaffolds and enhance binding affinity and selectivity through strategic functional group modifications. Molecular docking studies demonstrated strong binding of the selected derivatives to EGFR's ATP-binding site of EGFR. The docking scores revealed strong binding affinities, with compounds ۱۲, ۱۴, ۱۷, and ۱۸ showing the highest potential (-۱۰.۶, -۱۰.۶, -۱۰.۱, and -۱۰.۹ Kcal/mol, respectively) as EGFR kinase (PDB ID: ۱XKK) inhibitors because of their favorable docking scores and interactions with key residues. Based on Lipinski's rule and predictive computer models, the ADMET analysis showed that the compounds were well-liked, absorbed, distributed, metabolized, excreted, and had low toxicity. The persistent engagement of essential residues, including ASP۸۵۵, MET۷۶۶, and PHE۸۵۶, in both our research and existing literature underscores their pivotal function in EGFR inhibition. These results provide significant insights for directing future drug design efforts aimed at targeting EGFR kinase with the potential to develop more efficacious anticancer medicines. These findings highlight the potential of these compounds as effective and safe EGFR kinase inhibitors, warranting further in vitro and in vivo validations.

کلیدواژه ها:

EGFR Kinase inhibitor ، Cancer therapy ، Molecular docking ، ADMET analysis