Biological evaluation, docking studies, and in silico ADME prediction of some pyrimidine and pyridine derivatives as potential EGFR WT and EGFR T790M inhibitors.
Tarfah Al-WarhiAhmed Ali Al-KarmalawyAyman Abo ElmaatyMaha A AlshubramyMarwa Abdel-MotaalTaghreed A MajrashiMedhat AsemAhmed NabilWagdy M EldehnaMarwa SharakyPublished in: Journal of enzyme inhibition and medicinal chemistry (2022)
Herein, a set of pyridine and pyrimidine derivatives were assessed for their impact on the cell cycle and apoptosis. Human breast cancer (MCF7), hepatocellular carcinoma (HEPG2), larynx cancer (HEP2), lung cancer (H460), colon cancers (HCT116 and Caco2), and hypopharyngeal cancer (FADU), and normal Vero cell lines were used. Compounds 8 and 14 displayed outstanding effects on the investigated cell lines and were further tested for their antioxidant activity in MCF7, H460, FADU, HEP2, HEPG2, HCT116, Caco2, and Vero cells by measuring superoxide dismutase (SOD), malondialdehyde content (MDA), reduced glutathione (GSH), and nitric oxide (NO) content. Besides, Annexin V-FITC apoptosis detection and cell cycle DNA index using the HEPG-2 cell line were established on both compounds as well. Furthermore, compounds 8 and 14 were assessed for their EGFR kinase (Wild and T790M) inhibitory activities, revealing eligible potential. Additionally, molecular docking, ADME, and SAR studies were carried out for the investigated candidates.
Keyphrases
- cell cycle
- molecular docking
- cell cycle arrest
- cell death
- pi k akt
- molecular dynamics simulations
- cell proliferation
- small cell lung cancer
- tyrosine kinase
- epidermal growth factor receptor
- papillary thyroid
- nitric oxide
- breast cancer cells
- endothelial cells
- endoplasmic reticulum stress
- squamous cell
- induced apoptosis
- childhood cancer
- oxidative stress
- signaling pathway
- molecular dynamics
- case control
- atomic force microscopy
- lymph node metastasis
- risk assessment
- protein kinase
- nitric oxide synthase
- loop mediated isothermal amplification