当前位置: X-MOL 学术Bioorg. Med. Chem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Novel 2-amino-1,4-naphthoquinone hybrids: Design, synthesis, cytotoxicity evaluation and in silico studies
Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2020-08-28 , DOI: 10.1016/j.bmc.2020.115718
Maryam Gholampour 1 , Hassan Seradj 2 , Somayeh Pirhadi 3 , Mehdi Khoshneviszadeh 4
Affiliation  

In the present work, a novel series of 2-amino-1,4-naphthoquinones bearing oxyphenyl moiety (5a-5m) were designed and synthesized via a two-step route and evaluated for their in vitro cytotoxic activity against three different cancer cell lines (MCF-7, HL-60 and U937) and normal human cell line (HEK-293) by MTT assay. Compounds 5b (4-nitro-benzyl-) and 5k (4-bromo-benzyl-) were identified to possess the highest cytotoxic activity against MCF-7 cancerous cells (IC50 values of 27.76 and 27.86 μM, respectively). At the same time, none of the compounds exert significant toxicity against HEK-293 normal human kidney cells. Cell cycle analysis showed that the selected derivatives increased the population of MCF-7 cells in the S phase at 25 and 50 μM concentrations. Annexin V-FITC/PI staining assay also confirmed that compounds 5b and 5k induced apoptosis in the cell death pathway. Molecular docking and molecular dynamics studies were also performed to evaluate the probable interactions between the hybrids and human ATP binding domain of topo IIα protein. Our findings may provide new insight for further development of novel naphthoquinone-containing compounds.



中文翻译:

新型2-氨基-1,4-萘醌杂化物:设计,合成,细胞毒性评估和计算机模拟研究

在目前的工作中,设计并合成了一系列新颖的带有氧苯基部分的2-氨基-1,4-萘醌(5a-5m),并通过两步路线进行了合成,并评估了它们对三种不同癌细胞系的体外细胞毒活性。 (MTF-7,HL-60和U937)和正常人细胞系(HEK-293)进行MTT分析。化合物5b(4-硝基-苄基-)和5k(4-溴-苄基-)被鉴定为对MCF-7癌细胞具有最高的细胞毒活性(IC 50值分别为27.76和27.86μM)。同时,没有一种化合物对HEK-293正常人肾细胞有明显的毒性。细胞周期分析表明,所选的衍生物在25和50μM浓度下增加了S期MCF-7细胞的数量。Annexin V-FITC / PI染色测定法还证实化合物5b5k诱导了细胞死亡途径中的凋亡。还进行了分子对接和分子动力学研究,以评估杂种与topoIIα蛋白的人ATP结合域之间可能的相互作用。我们的发现可能为进一步开发新型萘醌化合物提供新的见解。

更新日期:2020-09-09
down
wechat
bug