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发光双(苯并[]噻唑基)喹喔啉:简便合成、核酸与蛋白质牛血清白蛋白相互作用、活细胞成像、生物制药研究及癌症诊疗应用

Luminescent bis(benzo[]thiazolyl)quinoxaline: facile synthesis, nucleic acid and protein BSA interaction, live-cell imaging, biopharmaceutical research and cancer theranostic application.

作者信息

Babu Lavanya Thilak, Jadhav Gajanan Raosaheb, Paira Priyankar

机构信息

Department of Chemistry, School of Advanced Sciences, Vellore Institute of Technology Vellore-632014 Tamilnadu India

Drug Metabolism and Pharmacokinetics, Eurofins Advinus Ltd. 21 & 22, Phase II, Peenya Industrial Area Bangalore 560058 India.

出版信息

RSC Adv. 2019 Mar 18;9(16):8748-8752. doi: 10.1039/c9ra01498e. eCollection 2019 Mar 15.

Abstract

A series of quinoxaline-2-hydroxyphenylbenzothiazole scaffolds were synthesized and characterized using NMR, UV, fluorescence spectroscopy and LCMS. These newly synthesized compounds were found to be cytotoxic in human epithelioid cervix carcinoma (HeLa) and human colon cancer cell lines (Caco-2). Selectivity of the compounds 7e and 7g are more than 9 fold higher in Caco-2 cells with respect to the normal cell line HEK-293. The most fluorescent compound 7e has displayed high cytoselectivity, significant cellular uptake in HeLa cells and strong binding efficacy with DNA and BSA. The most potent compound 7g has primarily classified as BCS class 4 and BDDCS class 4.

摘要

合成了一系列喹喔啉-2-羟基苯基苯并噻唑支架,并通过核磁共振(NMR)、紫外(UV)、荧光光谱和液相色谱-质谱联用(LCMS)对其进行了表征。发现这些新合成的化合物对人上皮样子宫颈癌(HeLa)细胞系和人结肠癌细胞系(Caco-2)具有细胞毒性。化合物7e和7g在Caco-2细胞中的选择性相对于正常细胞系HEK-293高出9倍以上。荧光最强的化合物7e表现出高细胞选择性、在HeLa细胞中有显著的细胞摄取以及与DNA和牛血清白蛋白(BSA)有强结合效力。最有效的化合物7g主要归类为生物药剂学分类系统(BCS)4类和生物药物处置分类系统(BDDCS)4类。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/973b/9061853/2d0a4b386051/c9ra01498e-f1.jpg

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