Benzofuran–appended 4-aminoquinazoline hybrids as epidermal growth factor receptor tyrosine kinase inhibitors: synthesis, biological evaluation and molecular docking studies

• Main Authors: Malose J. Mphahlele, Marole M. Maluleka, Abimbola Aro, Lyndy J. McGaw, Yee Siew Choong
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2018-01-01
• Series: Journal of Enzyme Inhibition and Medicinal Chemistry
• Subjects: Benzofuran-aminoquinazolines; cytotoxicity; apoptosis; EGFR-TK; molecular docking
• Online Access: http://dx.doi.org/10.1080/14756366.2018.1510919
• ISSN: 1475-6366; 1475-6374

A series of 2-arylbenzo[b]furan–appended 4-aminoquinazoline hybrids were prepared and evaluated for cytotoxicity in vitro against the human lung cancer (A549), colorectal adenocarcinoma (Caco-2), hepatocellular carcinoma (C3A) and cervical cancer (HeLa) cell lines. Compounds 10d and 10j exhibited significant cytotoxicity against the C3A and Caco-2 cell lines and induced apoptosis in these cell lines. Likewise, compounds 10d and 10e exhibited significant inhibitory activity towards epidermal growth factor receptor-tyrosine kinase phosphorylation (IC50 values of 29.3 nM and 31.1 nM, respectively) against Gefitinib (IC50 = 33.1 nM). Molecular docking of compounds 10 into EGFR-TK active site suggests that they bind to the region of EGFR like Gefitinib does.