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Molecules 2016, 21(10), 1366; doi:10.3390/molecules21101366

Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines

1
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa
2
Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa
*
Author to whom correspondence should be addressed.
Academic Editor: Philippe Belmont
Received: 30 August 2016 / Revised: 30 September 2016 / Accepted: 6 October 2016 / Published: 14 October 2016
(This article belongs to the Collection Heterocyclic Compounds)
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Abstract

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. View Full-Text
Keywords: 2-aryl-6-bromo-4-chloro-8-iodoquinazolines; amination; cross-coupling; polycarbo-substituted 4-anilinoquinazolines; cytotoxicity; apoptosis 2-aryl-6-bromo-4-chloro-8-iodoquinazolines; amination; cross-coupling; polycarbo-substituted 4-anilinoquinazolines; cytotoxicity; apoptosis
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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

Paumo, H.K.; Makhafola, T.J.; Mphahlele, M.J. Synthesis and In Vitro Cytotoxic Properties of Polycarbo-Substituted 4-(Arylamino)quinazolines. Molecules 2016, 21, 1366.

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