Abstract:
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.
