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

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.