Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents
Click chemistry based multicomponent approach in the synthesis of spirochromenocarbazole tethered 1,2,3-triazoles as potential anticancer agents
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DOI：
10.1016/j.bioorg.2019.01.070
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发表时间：
2019-04-01
影响因子：
5.1
通讯作者：
Sarkar, Dhiman
中科院分区：
文献类型：
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作者：
Chavan, Pramod, V;Desai, Uday, V;Sarkar, Dhiman
以N-炔丙基靛红、丙二腈、4-羟基咔唑、芳烷基卤和叠氮化钠为原料，纤维素负载CuI纳米粒子（Cell-CuI NPs）为非均相催化剂，通过点击化学一锅法五组分反应合成了一系列螺色烯并咔唑连接的1，2，3-三唑类化合物。研究了所有合成化合物对一组癌细胞系如MCF-7、MDA-MB-231、HeLa、PANG-1、A-549和THP-1的抗增殖活性。许多合成的化合物对乳腺癌（MCF-7和MDA-MB-231）和宫颈癌（HeLa）细胞表现出良好的抗增殖活性，IC 50值小于10 μ M。在MCF-7细胞的情况下，在显示出良好抗增殖活性的9种化合物中，发现化合物6 f和6 j是高度有效的（IC 50分别为2.13 μ M和4.80 μ M）。在MDA-MB-231的情况下，三种化合物（6 k、6 j和6s）显示出抗增殖活性，其中6 k是最有效的一种（IC 50 = 3.78 μ M）。另一方面，在宫颈癌HeLa细胞中，化合物6 b、6 g、6s和6 u显示出优异的抗增殖活性（IC 50分别= 4.05、3.54、3.83、3.35 μ M）。所有化合物对人脐静脉内皮细胞（HUVECs）均无毒性。活性化合物的AO和EtBr染色和荧光显微镜研究（IC 50 < 5 μ M）表明，这些化合物通过凋亡诱导细胞死亡。
A series of spirochromenocarbazole tethered 1,2,3-triazoles were synthesized via click chemistry based one-pot, five component reaction between N-propargyl isatins, malononitrile, 4-hydroxycarbazole, aralkyl halides and sodium azide using cellulose supported CuI nanoparticles (Cell-CuI NPs) as the heterogeneous catalyst. Antiproliferative activity of all the synthesized compounds was investigated against panel of cancer cell lines such as MCF-7, MDA-MB-231, HeLa, PANG-1, A-549, and THP-1. Many of the synthesized compounds exhibited good anti-proliferative activity against breast (MCF-7 and MDA-MB-231) and cervical (HeLa) cancer cells with IC50 values less than 10 mu M. In case of MCF-7 cells, among the nine compounds that showed good anti-proliferative activity, compounds 6f and 6j were found to be highly potent (IC50 , = 2.13 mu M and 4.80 mu M, respectively). In case of MDA-MB-231, three compounds (6k, 6j and 6s) showed antiproliferative activity amongst which 6k was the most potent one (IC50 = 3.78 mu M). On the other hand, in cervical cancer HeLa cells, compounds 6b, 6g, 6s and 6u showed excellent antiproliferative activity (IC50 = 4.05, 3.54, 3.83, 3.35 mu M, respectively). All the compounds were found to be nontoxic to the human umbilical vein endothelial cells (HUVECs). AO and EtBr staining and fluorescence microscopy studies of the active compounds (IC50 < 5 mu M) suggested that these compounds induce cell death by apoptosis.