Synthesis, Biological Evaluation and Molecular Docking of Novel Indole-Aminoquinazoline Hybrids for Anticancer Properties

• Main Authors: Malose J. Mphahlele, Mmakwena M. Mmonwa, Abimbola Aro, Lyndy J. McGaw, Yee Siew Choong
• Format: Article
• Language: English
• Published: MDPI AG 2018-07-01
• Series: International Journal of Molecular Sciences
• Subjects: indole-aminoquinazolines; cytotoxicity; apoptosis; EGFR-TK; molecular docking
• Online Access: http://www.mdpi.com/1422-0067/19/8/2232

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.