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基于醌的硼二吡咯杂化物的合成:关于癌细胞抗肿瘤活性及作用机制的新见解

On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells.

作者信息

Gontijo Talita B, de Freitas Rossimiriam P, Emery Flavio S, Pedrosa Leandro F, Vieira Neto José B, Cavalcanti Bruno C, Pessoa Claudia, King Aaron, de Moliner Fabio, Vendrell Marc, da Silva Júnior Eufrânio N

机构信息

Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.

Faculty of Pharmaceutical Sciences at Ribeirao Preto, University of São Paulo, CEP 14040-903, Ribeirão Preto, SP, Brazil.

出版信息

Bioorg Med Chem Lett. 2017 Sep 15;27(18):4446-4456. doi: 10.1016/j.bmcl.2017.08.007. Epub 2017 Aug 4.

Abstract

Fluorescent quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and mass spectrometry. We measured their cytotoxic activity against cancer and normal cell lines, performed mechanistic studies by lipid peroxidation and determination of reduced (GSH) and oxidized (GSSG) glutathione, and imaged their subcellular localisation by confocal microscopy. Cell imaging experiments indicated that nor-β-lapachone-based BODIPY derivatives might preferentially localise in the lysosomes of cancer cells. These results assert the potential of hybrid quinone-BODIPY derivatives as promising prototypes in the search of new potent lapachone antitumor drugs.

摘要

合成了基于荧光醌的BODIPY杂化物,并通过核磁共振分析和质谱对其进行了表征。我们测定了它们对癌细胞系和正常细胞系的细胞毒性活性,通过脂质过氧化以及还原型(GSH)和氧化型(GSSG)谷胱甘肽的测定进行了机理研究,并通过共聚焦显微镜对其亚细胞定位进行了成像。细胞成像实验表明,基于去甲-β-拉帕醌的BODIPY衍生物可能优先定位于癌细胞的溶酶体中。这些结果表明,醌-BODIPY杂化衍生物作为寻找新型强效拉帕醌抗肿瘤药物的有前景的原型具有潜力。

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