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

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),...

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Bibliographic Details
Published in:International journal of molecular sciences 2018-07, Vol.19 (8), p.2232
Main Authors: Mphahlele, Malose J, Mmonwa, Mmakwena M, Aro, Abimbola, McGaw, Lyndy J, Choong, Yee Siew
Format: Article
Language:English
Subjects:
Adenocarcinoma
Apoptosis
Aromatic compounds
Binding sites
Bioavailability
Cervical cancer
Cervix
Chromatography
Colorectal carcinoma
Cytotoxicity
EGFR-TK
Epidermal growth factor
Epidermal growth factor receptors
Gefitinib
Growth factors
Hepatocellular carcinoma
Hybrids
indole-aminoquinazolines
Indoles
Liver cancer
Lung cancer
Molecular docking
NMR
Nuclear magnetic resonance
Phosphorylation
Vascular endothelial growth factor
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Summary: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 ; 2-(4-fluorophenyl) and 3-chlorophenyl rings in compound ; or the two 2-(4-fluorophenyl) rings in compound , resulted in significant and moderate activity against the Caco-2 and C3A cell lines. The indole-aminoquinazoline hybrids compounds and induced apoptosis in Caco-2 and C3A cells, and were also found to exhibit moderate (IC = 52.5 nM) and significant (IC = 40.7 nM) inhibitory activity towards epidermal growth factor receptor (EGFR) against gefitinib (IC = 38.9 nM). Molecular docking suggests that 4a⁻h could bind to the ATP region of EGFR like erlotinib.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms19082232