Synthesis and biological evaluation of indazole derivatives as anti-cancer agents.
Synthesis and biological evaluation of indazole derivatives as anti-cancer agents.
复制标题
抗癌吲唑衍生物的合成及生物学评价
作者：
FDA批准的几种小分子抗癌药物含有吲唑支架。在此，我们报道了一系列吲唑衍生物的设计、合成和生物学评价。体外抗增殖活性筛选表明，化合物2f对多种癌细胞系具有有效的生长抑制活性（IC50 = 0.23–1.15 μM）。用2f处理乳腺癌细胞系4T1可抑制细胞增殖和集落形成。 2f剂量依赖性地促进4T1细胞的凋亡，这与cleaved caspase-3和Bax的上调以及Bcl-2的下调有关。 2f 还降低了 4T1 细胞中的线粒体膜电位并增加了活性氧 (ROS) 的水平。此外，2f处理破坏了4T1细胞的迁移和侵袭，还观察到基质金属蛋白酶金属蛋白酶9（MMP9）减少和组织抑制剂基质金属蛋白酶2（TIMP2）增加。此外，2f可以抑制4T1肿瘤模型的生长，并且在体内没有明显的副作用。综上所述，这些结果表明 2f 是一种潜在的小分子抗癌剂。
Several FDA approved small molecule anti-cancer drugs contain indazole scaffolds. Here, we report the design, synthesis and biological evaluation of a series of indazole derivatives. In vitro antiproliferative activity screening showed that compound 2f had potent growth inhibitory activity against several cancer cell lines (IC50 = 0.23–1.15 μM). Treatment of the breast cancer cell line 4T1 with 2f inhibited cell proliferation and colony formation. 2f dose-dependently promoted the apoptosis of 4T1 cells, which was connected with the upregulation of cleaved caspase-3 and Bax, and downregulation of Bcl-2. 2f also decreased the mitochondrial membrane potential and increased the levels of reactive oxygen species (ROS) in 4T1 cells. Additionally, treatment with 2f disrupted 4T1 cells migration and invasion, and the reduction of matrix metalloproteinase metalloproteinase-9 (MMP9) and increase of tissue inhibitor matrix metalloproteinase 2 (TIMP2) were also observed. Moreover, 2f could suppress the growth of the 4T1 tumor model without obvious side effects in vivo. Taken together, these results identified 2f as a potential small molecule anti-cancer agent.
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影响因子：
4.6
作者：
Solano LN;Nelson GL;Ronayne CT;Jonnalagadda S;Jonnalagadda SK;Kottke K;Chitren R;Johnson JL;Pandey MK;Jonnalagadda SC;Mereddy VR
通讯作者：
Mereddy VR
影响因子：
0.9
作者：
Reddy, G. Sandeep;Mohanty, S.;Rao, B. Venteswar
通讯作者：
Rao, B. Venteswar
抗癌剂多卤代2-芳基-4-氨基喹唑啉和3-氨基吲唑的合成
影响因子：
3.9
作者：
Yan, Sheng-Jiao;Dong, Ying;Lin, Jun
通讯作者：
Lin, Jun
DOI：
10.3390/molecules23112783
发表时间：
2018-10-26
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Zhang SG;Liang CG;Zhang WH
通讯作者：
Zhang WH
影响因子：
7.3
作者：
Sampson, Peter B.;Liu, Yong;Pauls, Henry W.
通讯作者：
Pauls, Henry W.