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
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 o...
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doaj-9bd1cf6b7b5c4fa2a89c998780caa8ab2020-11-25T03:46:44ZengMDPI AGPharmaceuticals1424-82472017-11-011048710.3390/ph10040087ph10040087Synthesis 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 KinaseMalose Jack Mphahlele0Hugues K. Paumo1Yee Siew Choong2Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaDepartment of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaInstitute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang 11800, MalaysiaSeries 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.https://www.mdpi.com/1424-8247/10/4/876-bromo-4-chloroquinazolinesaminationSuzuki–Miyaura cross-couplingcytotoxicityEGFR-TKmolecular docking |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Malose Jack Mphahlele Hugues K. Paumo Yee Siew Choong |
spellingShingle |
Malose Jack Mphahlele Hugues K. Paumo Yee Siew Choong 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 6-bromo-4-chloroquinazolines amination Suzuki–Miyaura cross-coupling cytotoxicity EGFR-TK molecular docking |
author_facet |
Malose Jack Mphahlele Hugues K. Paumo Yee Siew Choong |
author_sort |
Malose Jack Mphahlele |
title |
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 |
title_short |
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 |
title_full |
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 |
title_fullStr |
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 |
title_full_unstemmed |
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 |
title_sort |
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 |
publisher |
MDPI AG |
series |
Pharmaceuticals |
issn |
1424-8247 |
publishDate |
2017-11-01 |
description |
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. |
topic |
6-bromo-4-chloroquinazolines amination Suzuki–Miyaura cross-coupling cytotoxicity EGFR-TK molecular docking |
url |
https://www.mdpi.com/1424-8247/10/4/87 |
work_keys_str_mv |
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