Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities.
Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities.
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双(吲哚基)乙醛酰胺的连续一锅合成：抗菌和抗癌活性评价。
DOI：
10.1016/j.bmcl.2016.04.080
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发表时间：
2016
影响因子：
2.7
通讯作者：
Kumar,Dalip
中科院分区：
文献类型：
--
作者：
Tantak,MukundP;Gupta,Vishakha;Nikhil,Kumar;Arun,V;Singh,RajnishPrakash;Jha,PrabhatNath;Shah,Kavita;Kumar,Dalip
设计并合成了一系列双吲哚基甘氨酰胺10a-n。吲哚9与草酰氯反应原位生成吲哚-3-乙二醛酰氯，经色胺处理，得到双吲哚基甘氨酰胺10a，产率82-93%。所有合成的双（吲哚基）甘氨酰胺被很好地表征，并测试其对革兰氏阳性和革兰氏阴性细菌菌株的抗菌活性。化合物10 d、10和10 i对革兰氏阴性菌有较强的抗菌活性。此外，针对一组人癌细胞系评价了双（吲哚基）甘氨酰胺10a-n的细胞毒性。在筛选的类似物中，化合物10 f（IC 50 = 22.34 μM; HeLa，24.05 μM; PC-3，21.13 μM; MDA-MB-231和29.94 μM; BxPC-3）被鉴定为该系列中最有效的类似物。PC-3细胞暴露于10 μ g/10 μ f导致裂解的PARP 1水平增加，表明双（吲哚基）甘氨酰胺诱导PC-3细胞凋亡。最重要的是，化合物10 d、10和10 i在哺乳动物细胞中完全无效，表明它们靶向细菌特异性靶标，因此在宿主细胞中不会显示任何毒性。
A series of bis(indolyl)glyoxylamides10a–nhas been designed and synthesized. In situ generated indole-3-glyoxalylchloride from the reaction of readily available indole9with oxalyl chloride was treated with tryptamine to produce bis(indolyl)glyoxylamides10a–nin 82–93% yields. All the synthesized bis(indolyl)glyoxylamides were well characterized and tested for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Compounds10d,10gand10iwere found to display potent antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides10a–nwere evaluated against a panel of human cancer cell lines. Of the screened analogues, compound10f(IC50= 22.34 μM; HeLa, 24.05 μM; PC-3, 21.13 μM; MDA-MB-231 and 29.94 μM; BxPC-3) was identified as the most potent analogue of the series. Exposure of PC-3 cells to either10aor10fresulted in increased levels of cleaved PARP1, indicating that bis(indolyl)glyoxylamides induce apoptosis in PC-3 cells. Most importantly, compounds10d,10gand10iwere completely ineffective in mammalian cells, suggesting that they target bacterial-specific targets and thus will not display any toxicity in host cells.