Abstract
11C-1-aminocyclobutane carboxylic acid (ACBC) an unnatural cyclic amino carboxylic acid, has been reported previously to be high accurate in determining recurrent brain tumors. This work has synthesized a lipophilic boron-containing cyclic amino carboxylic acid, 1-amino-3-[7-(4-borophenyl)heptyl]cyclobutane carboxylic acid, analogous to ACBC, as a BNCT drug for treatment to brain tumors and hepatoma. In the present study, cell uptake of the boron-containing amino acid in hepatoma and glioblastoma has been investigated.1-Amino-3-(4-boronophenyl)cyclobutane carboxylic acid has been successfully synthesized via 7 steps. The key synthetic process is pertinent to the initial two steps; the reaction will become incomplete and lead to very low product-yield if the moisture exists. The last two steps involve the preparation of properly substituted cyclobutanone followed by a Bucherer-Strecker amino acid synthesis. The final product in a mixture with NaCl is tried to purify by a silica gel column chromatography. All products were identified by 1H-NMRand13C-NMR.The products obtained from the synthesis 3-(4-boronophenyl)cyclobutanone(compound Ⅵ) and 1-amino-3-(4-boronophenyl)cyclo-butanecarboxylic acid(compound Ⅷ) were taken for the cell uptake test by glioblastoma （G5T/VGH and GBM8901 tumor cell）and hepatoma（HepG2 tumor cell）. Experiments with respect to maximal lethal dose (LD50), chemical toxicity, radiation damage, and cell uptake extent are conducted.Comparing the toxicity of both boron containing compounds, the 50% lethal dose of 3-(4-boronophenyl)cyclobutanone (Ⅵ) for the tumor cells of either hepatoma or glioblastoma is generaly lower than 1-amino-3-(4-boronophenyl)cyclobutane carboxylic acid(Ⅷ). For HepG2 cells, 50% lethal dose for compound Ⅵ is 150 ppm, while for compound Ⅷ is 1000 ppm. For GBM8901 cells, 50% lethal dose for compound Ⅵ is 400 ppm, while for compound Ⅷ is 4000 ppm. For G5TVGH cells, 50% lethal dose for compound Ⅵ is 200 ppm, while for compound Ⅷ is 700 ppm.The uptake of compound Ⅵ by HepG2 cells was observed to increase with increasing the elapsed time, reaching 2.7×1014 B/cell at 48 h, while the uptake of compound Ⅷ by HepG2 cells was negligible. By contrast, the uptake of compound Ⅷ by GBM8901 cells was observed to increase initially to 4×1013 B/cell at 3 h and then decrease with increasing the elapsed time to 6.5×1011 B/cell at 48h. While the uptake of compound Ⅷ by G5T/VGH cells was observed to increase initially to 7.47×1012 B/cell at 6 h and then decrease with increasing the elapsed time to 3.59×1012 B/cell at 24h. From the results, it is revealed that compound Ⅵ may possess the potential as hepatoma BNCT drug, while compound Ⅷ may have the potential as glioblastoma BNCT drug.