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Potent antiproliferative active agents: novel bis Schiff bases and bis spiro β-lactams bearing isatin tethered with butylene and phenylene as spacer and DNA/BSA binding behavior as well as studying molecular docking
Medicinal Chemistry Research ( IF 2.6 ) Pub Date : 2020-11-11 , DOI: 10.1007/s00044-020-02659-5
Mohammad Bashiri , Aliasghar Jarrahpour , S. Masoud Nabavizadeh , Somaye Karimian , Banafsheh Rastegari , Elahe Haddadi , Edward Turos

A [2+2]-cycloaddition of bis-isatin Schiff bases 5a–b and 7 with activated aryloxyacetic acid derivatives 8a–d afforded bis-spiroisatino β-lactams with aliphatic and aromatic spacers. The structures of the synthesized 2-oxindoles and spirooxindoles were determined based on Fourier-transform infrared spectroscopy, proton-1 and carbon-13 nuclear magnetic resonance spectroscopies and CHN analysis. Our interest in these bis-Schiff bases and bis-spiroisatino β-lactams is for their potential anticancer capabilities. In vitro bioactivity testing against the cervical adenocarcinoma (HeLa) and breast cancer (MCF-7) cell lines as well as noncancerous NIH/3T3 fibroblast cell was investigated applying the MTT assay. Bis-isatin derivatives 5a, 5b, 9h, 10a, and 10b showed promising antiproliferative activity toward these two cancer cell lines. Two of the bis-isatin Schiff bases, 5a and 5b, displayed IC50 values less than that of the clinically-used anticancer agent cisplatin towards both the MCF-7 and HeLa cells, while several of the bis-isatin β-lactams showed similar bioactivity to that of cisplatin. All of the oxindoles and spirooxindoles displayed a selective anticancer effect except 10b. To study the possible mechanism for this bioactivity, DNA and BSA binding analyses were performed using fluorescence and UV–visible spectroscopic techniques. The isatin adducts displayed excellent interaction propensity to CT-DNA as well as BSA. Molecular docking investigation carried out on DNA and BSA with promising molecules to show the possible mechanism of cytotoxicity activities.



中文翻译:

强大的抗增殖活性剂:新型的双席夫碱和双螺旋β-内酰胺,带有以丁烯和亚苯基为间隔基的isatin分子,并与DNA / BSA结合,并研究了分子对接

双-isatin Schiff碱5a-b7与活化的芳氧基乙酸衍生物8a-进行[2 + 2]-环加成反应,可得到带有脂肪族和芳香族间隔基的双-螺脲基β-内酰胺。基于傅立叶变换红外光谱,质子1和碳13核磁共振光谱以及CHN分析,确定了合成的2-氧吲哚和螺氧并吲哚的结构。我们对这些双席夫碱和双螺旋藻β-内酰胺的兴趣在于其潜在的抗癌能力。应用MTT法研究了针对宫颈腺癌(HeLa)和乳腺癌(MCF-7)细胞系以及非癌NIH / 3T3成纤维细胞的体外生物活性测试。双isatin衍生物5a图5b9h10a10b显示出对这两种癌细胞的有希望的抗增殖活性。双-isatin Schiff碱中的两个5a5b对MCF-7和HeLa细胞显示的IC 50值低于临床上使用的抗癌药顺铂的IC 50值,而一些双-isatinβ-内酰胺类药物显示出相似的IC 50值。顺铂的生物活性。除10b以外,所有的羟吲哚和螺菌毒素都显示出选择性的抗癌作用。为了研究这种生物活性的可能机制,使用荧光和紫外可见光谱技术进行了DNA和BSA结合分析。靛红加合物对CT-DNA和BSA具有极好的相互作用倾向。对DNA和BSA与有前途的分子进行了分子对接研究,以显示其细胞毒性活性的可能机制。

更新日期:2020-11-12
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