Paumo Hugues Kamdem, Makhafola Tshepiso Jan, Mphahlele Malose Jack
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa.
Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa.
Molecules. 2016 Oct 14;21(10):1366. doi: 10.3390/molecules21101366.
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, , , , , and , were found to be more selective against the MCF-7 and HeLa cell lines than the human lung carcinoma (A549) cells. We selected compounds , and as representatives for further evaluation for potential to induce apoptosis and/or necrotic properties in the three cancer cell lines. Compound induced apoptosis of MCF-7 cells through cell membrane alteration. Treatment of Hela and A549 cell lines with compounds and , respectively, led to caspase-3 activation in both cell lines. Compound , on the other hand, caused more necrosis than apoptosis induction in the membrane alteration assay.
在此，我们描述了通过一锅三步反应序列合成新型不对称多碳取代的4-苯胺基喹唑啉，该反应序列包括初始胺化以及随后与不同交叉偶联伙伴进行的双交叉偶联（双铃木反应、Sonogashira/Stille反应或Sonogashira/Suzuki-Miyaura反应），用于形成两个碳-碳键。对4-苯胺基喹唑啉针对三种癌细胞系，即人乳腺腺癌（MCF-7）细胞、人宫颈癌（HeLa）细胞和人肺癌（A549）细胞，进行了潜在细胞毒性评估。发现活性最高的化合物，即 、 、 、 、 和 ，对MCF-7和HeLa细胞系的选择性高于人肺癌（A549）细胞。我们选择化合物 、 和 作为代表，进一步评估其在三种癌细胞系中诱导凋亡和/或坏死特性的潜力。化合物 通过改变细胞膜诱导MCF-7细胞凋亡。分别用化合物 和 处理HeLa和A549细胞系，导致两种细胞系中的半胱天冬酶-3激活。另一方面，在细胞膜改变试验中，化合物 引起的坏死比凋亡更多。
