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Pharmaceuticals 2017, 10(4), 87; doi:10.3390/ph10040087

Synthesis and In Vitro Cytotoxicity of the 4-(Halogenoanilino)-6-bromoquinazolines and Their 6-(4-Fluorophenyl) Substituted Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor Tyrosine Kinase

1
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa
2
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang 11800, Malaysia
*
Author to whom correspondence should be addressed.
Received: 21 September 2017 / Revised: 29 October 2017 / Accepted: 31 October 2017 / Published: 20 November 2017
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Abstract

Series of the 2-unsubstituted and 2-(4-chlorophenyl)–substituted 4-anilino-6-bromoquinazolines and their 6-(4-fluorophenyl)–substituted derivatives were evaluated for in vitro cytotoxicity against MCF-7 and HeLa cells. The 2-unsubstituted 4-anilino-6-bromoquinazolines lacked activity, whereas most of their 2-(4-chlorophenyl) substituted derivatives were found to exhibit significant cytotoxicity and selectivity against HeLa cells. Replacement of bromine with 4-fluorophenyl group for the 2-unsubstituted 4-anilinoquinazolines resulted in superior activity against HeLa cells compared to Gefitinib. The presence of a 4-fluorophenyl group in the 2-(4-chlorophenyl) substituted derivatives led to increased cytotoxicity against HeLa cells, except for the 3-chloroanilino derivative. The most active compounds, namely, 3g, 3l, and 4l, were found to exhibit a moderate to significant inhibitory effect against epidermal growth factor receptor tyrosine kinase (EGFR-TK). The EGFR molecular docking model suggested that these compounds are nicely bound to the region of EGFR. View Full-Text
Keywords: 6-bromo-4-chloroquinazolines; amination; Suzuki–Miyaura cross-coupling; cytotoxicity; EGFR-TK; molecular docking 6-bromo-4-chloroquinazolines; amination; Suzuki–Miyaura cross-coupling; cytotoxicity; EGFR-TK; molecular docking
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mphahlele, M.J.; Paumo, H.K.; Choong, Y.S. Synthesis and In Vitro Cytotoxicity of the 4-(Halogenoanilino)-6-bromoquinazolines and Their 6-(4-Fluorophenyl) Substituted Derivatives as Potential Inhibitors of Epidermal Growth Factor Receptor Tyrosine Kinase. Pharmaceuticals 2017, 10, 87.

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