Investigation of 𝑁-(5-nitrothiazol-2-yl)-2-((4-oxo-3,4-Dihydroquinazolin-2-yl) Thio) Acetamide Derivatives as Potential EGFR Kinase Inhibitors
نویسندگان
1 Department of Pharmacology, Aditya Pharmacy College (A), ADB Road, Surampalem, Andhra Pradesh, India
2 Royal College of Pharmacy and Health Sciences, Berhampur Odisha, India
3 College of Pharmaceutical Sciences, Marine Drive Road, Puri Odisha, India
4 Department of Pharmaceutical Chemistry, Narayan Institute of Pharmacy, Gopal Narayan Singh University, Jamuhar, Sasaram (Rohtas) Bihar, India
5 Research Scholar Annamalai University, Chidambaram, East Point College of Pharmacy, Virgo Nagar Post Bangalore, India
6 Department of Pharmacology, Arulmigu Kalasalingam College of Pharmacy, Krishnankoil, Tamilnadu, India
7 Department of Pharmaceutical Chemistry, Arulmigu kalasalingam college of Pharmacy, Krishnakoil, Tamil Nadu, India
8 Department of pharmaceutics, School of Pharmacy, Anurag University, Hyderabad, India
9 School of Pharmacy, Anurag University, Venkatapur, Ghatkesar Rd, Hyderabad Telangana, India
doi
10.48309/ajca.2025.504108.1779چکیده
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-(5-nitrothiazol-2-yl)-2-((4-oxo-3,4-dihydroquinazolin-2-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 12, 14, 17, and 18 showing the highest potential (-10.6, -10.6, -10.1, and -10.9 Kcal/mol, respectively) as EGFR kinase (PDB ID: 1XKK) 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 ASP855, MET766, and PHE856, 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.
