Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines
Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonoga...
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doaj-fa7e06d5fad04e6aab4dafbfc3066e322020-11-25T00:12:16ZengMDPI AGMolecules1420-30492016-10-012110136610.3390/molecules21101366molecules21101366Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolinesHugues Kamdem Paumo0Tshepiso Jan Makhafola1Malose Jack Mphahlele2Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South AfricaDepartment of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, 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 AfricaHerein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps. The 4-anilinoquinazolines were evaluated for potential cytotoxicity against three cancer cell lines, namely, human breast adenocarcinoma (MCF-7) cells, human cervical cancer (HeLa) and human lung cancer (A549) cells. The most active compounds, 2b, 2c, 3c, 4a, 4c and 5a, were found to be more selective against the MCF-7 and HeLa cell lines than the human lung carcinoma (A549) cells. We selected compounds 2c, 3c and 7a as representatives for further evaluation for potential to induce apoptosis and/or necrotic properties in the three cancer cell lines. Compound 2c induced apoptosis of MCF-7 cells through cell membrane alteration. Treatment of Hela and A549 cell lines with compounds 3c and 7a, respectively, led to caspase-3 activation in both cell lines. Compound 3c, on the other hand, caused more necrosis than apoptosis induction in the membrane alteration assay.http://www.mdpi.com/1420-3049/21/10/13662-aryl-6-bromo-4-chloro-8-iodoquinazolinesaminationcross-couplingpolycarbo-substituted 4-anilinoquinazolinescytotoxicityapoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hugues Kamdem Paumo Tshepiso Jan Makhafola Malose Jack Mphahlele |
spellingShingle |
Hugues Kamdem Paumo Tshepiso Jan Makhafola Malose Jack Mphahlele Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines Molecules 2-aryl-6-bromo-4-chloro-8-iodoquinazolines amination cross-coupling polycarbo-substituted 4-anilinoquinazolines cytotoxicity apoptosis |
author_facet |
Hugues Kamdem Paumo Tshepiso Jan Makhafola Malose Jack Mphahlele |
author_sort |
Hugues Kamdem Paumo |
title |
Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines |
title_short |
Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines |
title_full |
Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines |
title_fullStr |
Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines |
title_full_unstemmed |
Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines |
title_sort |
synthesis and in vitro cytotoxic properties of polycarbo-substituted 4-(arylamino)quinazolines |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2016-10-01 |
description |
Herein, we describe the synthesis of novel unsymmetrical polycarbo-substituted 4-anilinoquinazolines derived from the 2-aryl-6-bromo-8-iodoquinazolines via one-pot three-step reaction sequences involving initial amination and subsequent double cross-coupling (bis-Suzuki, Sonogashira/Stille or Sonogashira/Suzuki-Miyaura) reactions with different cross coupling partners for the two carbon–carbon bond formation steps. The 4-anilinoquinazolines were evaluated for potential cytotoxicity against three cancer cell lines, namely, human breast adenocarcinoma (MCF-7) cells, human cervical cancer (HeLa) and human lung cancer (A549) cells. The most active compounds, 2b, 2c, 3c, 4a, 4c and 5a, were found to be more selective against the MCF-7 and HeLa cell lines than the human lung carcinoma (A549) cells. We selected compounds 2c, 3c and 7a as representatives for further evaluation for potential to induce apoptosis and/or necrotic properties in the three cancer cell lines. Compound 2c induced apoptosis of MCF-7 cells through cell membrane alteration. Treatment of Hela and A549 cell lines with compounds 3c and 7a, respectively, led to caspase-3 activation in both cell lines. Compound 3c, on the other hand, caused more necrosis than apoptosis induction in the membrane alteration assay. |
topic |
2-aryl-6-bromo-4-chloro-8-iodoquinazolines amination cross-coupling polycarbo-substituted 4-anilinoquinazolines cytotoxicity apoptosis |
url |
http://www.mdpi.com/1420-3049/21/10/1366 |
work_keys_str_mv |
AT hugueskamdempaumo synthesisandinvitrocytotoxicpropertiesofpolycarbosubstituted4arylaminoquinazolines AT tshepisojanmakhafola synthesisandinvitrocytotoxicpropertiesofpolycarbosubstituted4arylaminoquinazolines AT malosejackmphahlele synthesisandinvitrocytotoxicpropertiesofpolycarbosubstituted4arylaminoquinazolines |
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