Xuan Sunting, Zhao Ning, Zhou Zehua, Fronczek Frank R, Vicente M Graça H
Department of Chemistry, Louisiana State University , Baton Rouge, Louisiana 70803, United States.
J Med Chem. 2016 Mar 10;59(5):2109-17. doi: 10.1021/acs.jmedchem.5b01783. Epub 2016 Feb 17.
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.
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。
