Synthesis, Biological Evaluation and Molecular Docking of Novel Indole-Aminoquinazoline Hybrids for Anticancer Properties.
Malose Jack MphahleleMmakwena M MmonwaAbimbola AroLyndy J McGawYee Siew ChoongPublished in: International journal of molecular sciences (2018)
A series of indole-aminoquinazolines was prepared via amination of the 2-aryl-4-chloroquinazolines with the 7-amino-2-aryl-5-bromoindoles. It was then evaluated for cytotoxicity in vitro against human lung cancer (A549), epithelial colorectal adenocarcinoma (Caco-2), hepatocellular carcinoma (C3A), breast adenocarcinoma (MCF-7), and cervical cancer (HeLa) cells. A combination on the quinazoline and indole moieties of a 2-phenyl and 2-(4-fluorophenyl) rings in compound 4b; 2-(4-fluorophenyl) and 3-chlorophenyl rings in compound 4f; or the two 2-(4-fluorophenyl) rings in compound 4g, resulted in significant and moderate activity against the Caco-2 and C3A cell lines. The indole-aminoquinazoline hybrids compounds 4f and 4g induced apoptosis in Caco-2 and C3A cells, and were also found to exhibit moderate (IC50 = 52.5 nM) and significant (IC50 = 40.7 nM) inhibitory activity towards epidermal growth factor receptor (EGFR) against gefitinib (IC50 = 38.9 nM). Molecular docking suggests that 4a⁻h could bind to the ATP region of EGFR like erlotinib.
Keyphrases
- epidermal growth factor receptor
- induced apoptosis
- molecular docking
- endoplasmic reticulum stress
- tyrosine kinase
- advanced non small cell lung cancer
- signaling pathway
- oxidative stress
- molecular dynamics simulations
- small cell lung cancer
- cell cycle arrest
- photodynamic therapy
- squamous cell carcinoma
- endothelial cells
- high intensity
- radiation therapy
- pi k akt
- light emitting