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用于快速声合成新型系列喹唑啉-4-酮衍生物作为潜在抗癌剂的深共熔溶剂

Deep eutectic solvent for an expeditious sono-synthesis of novel series of -quinazolin-4-one derivatives as potential anti-cancer agents.

作者信息

Ahmed Arafa Wael Abdelgayed

机构信息

Chemistry Department, College of Science, Jouf University, PO Box 2014, Sakaka, Aljouf, Kingdom of Saudi Arabia.

Chemistry Department, Faculty of Science, Fayoum University, PO Box 63514, Fayoum City, Egypt.

出版信息

R Soc Open Sci. 2019 Mar 20;6(3):182046. doi: 10.1098/rsos.182046. eCollection 2019 Mar.

Abstract

To produce a new category of anti-cancer compounds, a facile and environmentally sustainable method for preparing diversified -quinazolinones was demonstrated using recyclable deep eutectic solvent (DES) under ultrasonic irradiation. The reactions were performed smoothly with a wide scope of substrates affording the desired derivatives in good-to-excellent yields under an atom-economical pathway. Particularly, halogen substituents that are amenable for further synthetic elaborations are well tolerated. Furthermore, the 'greenness' of the protocol was assessed within the scope of several green metrics and found to display an excellent score in the specified parameters. Cytotoxic activity of all novel -quinazolinones was investigated utilizing two cancer cell lines: breast (MCF-7) and lung (A549) cell lines and their IC values were determined. Most of the prepared derivatives displayed fascinating inhibitory activity with IC values in a low micromolar range. Remarkably, the derivative [3,3'-(sulfonyl(4,1-phenylene))(2-methyl-6-nitroquinazolin-4(3)-one)] showed superior potency against MCF-7 and A549 cancer cell lines, with IC values of 1.26 µM and 2.75 µM, respectively. Moreover, this derivative was found to have low toxicity to the normal breast cell line (MCF-10A) and could serve as a promising lead candidate for further development.

摘要

为了制备一类新型抗癌化合物,展示了一种简便且环境可持续的方法,即在超声辐射下使用可回收的深共熔溶剂(DES)制备多样化的喹唑啉酮。反应在原子经济途径下顺利进行,底物范围广泛,能以良好至优异的产率得到所需衍生物。特别地,易于进行进一步合成修饰的卤素取代基具有良好的耐受性。此外,在几个绿色指标范围内评估了该方案的“绿色程度”,发现在指定参数中表现出优异的分数。利用两种癌细胞系:乳腺癌(MCF - 7)和肺癌(A549)细胞系研究了所有新型喹唑啉酮的细胞毒性活性,并测定了它们的IC值。大多数制备的衍生物表现出迷人的抑制活性,IC值在低微摩尔范围内。值得注意的是,衍生物[3,3'-(磺酰基(4,1-亚苯基))(2-甲基-6-硝基喹唑啉-4(3)-酮)]对MCF - 7和A549癌细胞系表现出优异的效力,IC值分别为1.26 μM和2.75 μM。此外,发现该衍生物对正常乳腺细胞系(MCF - 10A)毒性低,可作为进一步开发的有前景的先导候选物。

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