Synthesis and in Vitro Studies of a Series of Carborane-Containing Boron Dipyrromethenes (BODIPYs)

被引：49

作者：

Xuan, Sunting ^{[1
]}

Zhao, Ning ^{[1
]}

Zhou, Zehua ^{[1
]}

Fronczek, Frank R. ^{[1
]}

Vincente, M. Graca H. ^{[1
]}

机构：

[1] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 59卷 / 05期

基金：

美国国家卫生研究院;

关键词：

BLOOD-BRAIN-BARRIER; NEUTRON-CAPTURE THERAPY; ENDOTHELIAL-CELL LINE; PERMEABILITY; MODEL; DRUG; ANALOGS; CANCER;

D O I：

10.1021/acs.jmedchem.5b01783

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of seven BODIPYs functionalized with ortho-carborane groups at the 8(meso) or 3/5(alpha) 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 513 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 (P-e = 16.4 x 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.

引用

页码：2109 / 2117

页数：9

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