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新型喹诺酮骨架类抗癌药物的制备与纳米制剂:提高溶解度以实现更好的细胞递送

Preparation and nanoformulation of new quinolone scaffold-based anticancer agents: Enhancing solubility for better cellular delivery.

作者信息

Elghazawy Nehal H, Hefnawy Amr, Sedky Nada K, El-Sherbiny Ibrahim M, Arafa Reem K

机构信息

University of Science and Technology, Zewail City of Science and Technology, 12588 Giza, Egypt.

Center for Materials Science, Zewail City of Science and Technology, 6th October City, 12588, Giza, Egypt.

出版信息

Eur J Pharm Sci. 2017 Jul 15;105:203-211. doi: 10.1016/j.ejps.2017.05.036. Epub 2017 May 17.

Abstract

A new series of 5,7-dibromoquinoline scaffold-based derivatives with varied flexibility substituents at position 8 of the ring system has been synthesized as potential anticancer agents. The new compounds were evaluated for their in vitro antiproliferative activity versus the human breast cancer cell lines MCF-7 and MDA-MB231. Generally, both cell lines were responsive to the cytotoxic effect of the synthesized analogues. Compounds 4a, 5c and 7b were chosen for nanoformulation studies to assess the effect of enhancing their solubility profile on their cytotoxic ability. Indeed, the pluronic nanomicelles of the three formulated derivatives showed an observable significant increase in their cytotoxic efficacy demonstrating a positive impact of the used nanoformulations on the delivery of the active compounds to their cellular biological targets.

摘要

已经合成了一系列新的基于5,7-二溴喹啉骨架的衍生物,这些衍生物在环系统的8位具有不同的柔性取代基,作为潜在的抗癌剂。评估了这些新化合物对人乳腺癌细胞系MCF-7和MDA-MB231的体外抗增殖活性。一般来说,这两种细胞系对合成类似物的细胞毒性作用都有反应。选择化合物4a、5c和7b进行纳米制剂研究,以评估改善其溶解度对其细胞毒性能力的影响。事实上,三种制剂衍生物的普朗尼克纳米胶束的细胞毒性功效显著增加,表明所用纳米制剂对活性化合物向其细胞生物学靶点的递送有积极影响。

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