一系列含碳硼烷的硼二吡咯亚甲基（BODIPYs）的合成及体外研究
Synthesis and in Vitro Studies of a Series of Carborane-Containing Boron Dipyrromethenes (BODIPYs).
作者信息
Xuan Sunting, Zhao Ning, Zhou Zehua, Fronczek Frank R, Vicente M Graça H
机构信息
Department of Chemistry, Louisiana State University , Baton Rouge, Louisiana 70803, United States.
出版信息
J Med Chem. 2016 Mar 10;59(5):2109-17. doi: 10.1021/acs.jmedchem.5b01783. Epub 2016 Feb 17.
Abstract
A series of seven BODIPYs functionalized with ortho-carborane groups at the 8(meso) or 3/5(α) position were synthesized and characterized by NMR, HRMS, HPLC, and in the cases of 2b and 5b, by X-ray analysis. The BODIPYs exhibited low dark toxicity and phototoxicity toward human glioma T98G cells, and their cellular uptake varied significantly, with 5b accumulating the most and 7 the least. All BODIPYs localized mainly within the cell ER. The BODIPYs showed higher permeabilities than lucifer yellow across human hCMEC/D3 brain endothelial cell monolayers as the BBB model. Among this series, 1b showed the highest BBB permeability (Pe = 16.4 × 10(-5) cm/s), probably as a result of its lower MW (366 Da) and favorable hydrophobicity (log P = 1.5). The combination of low cytotoxicity, amphiphilicity, high boron content, high cellular uptake, and moderate BBB permeability renders these compounds promising boron delivery agents for the BNCT of brain tumors.
摘要
合成了一系列在8（中位）或3/5（α）位带有邻碳硼烷基团的七个BODIPY，并通过核磁共振（NMR）、高分辨质谱（HRMS）、高效液相色谱（HPLC）进行表征，对于2b和5b，还通过X射线分析进行了表征。这些BODIPY对人胶质瘤T98G细胞表现出低暗毒性和光毒性，并且它们的细胞摄取差异显著，5b积累最多，7积累最少。所有BODIPY主要定位于细胞内质网。作为血脑屏障（BBB）模型，BODIPY在人hCMEC/D3脑内皮细胞单层上显示出比荧光素黄更高的通透性。在该系列中，1b显示出最高的BBB通透性（Pe = 16.4×10⁻⁵ cm/s），这可能是由于其较低的分子量（366 Da）和良好的疏水性（log P = 1.5）。低细胞毒性、两亲性、高硼含量、高细胞摄取和适度的BBB通透性的组合使这些化合物成为用于脑肿瘤硼中子俘获疗法（BNCT）的有前景的硼递送剂。
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