New 6-nitro-4-substituted quinazoline derivatives targeting epidermal growth factor receptor: design, synthesis and in vitro anticancer studies.
Ayman B FaragAya H OthmanMohamed Kandeel El-AshreySafinaz E-S AbbasTamer A ElwaiePublished in: Future medicinal chemistry (2024)
Aim: Twenty compounds of 6-nitro-4-substituted quinazolines were synthesized. Materials & methods: The new derivatives were evaluated for their epidermal growth factor receptor (EGFR) inhibitory activity. The most potent derivatives were assessed for their cytotoxicity against colon cancer and lung cancer cells, in addition to normal fibroblast cells. Results & discussion: compound 6c showed a superior to nearly equal cytotoxicity in comparison to gefitinib, it also revealed a good safety profile. Compound 6c caused a cell cycle arrest at G2/M phase in addition to induction of apoptosis. A molecular docking study was conducted on the most active compounds to gain insights of their binding mode in the active site of EGFR enzyme besides ADME prediction of their physicochemical properties and drug likeness profile.
Keyphrases
- epidermal growth factor receptor
- molecular docking
- cell cycle arrest
- cell death
- tyrosine kinase
- pi k akt
- advanced non small cell lung cancer
- molecular dynamics simulations
- structure activity relationship
- signaling pathway
- single cell
- oxidative stress
- cell proliferation
- cancer therapy
- induced apoptosis
- emergency department
- endoplasmic reticulum stress
- dna binding
- anti inflammatory