Synthesis and biological evaluation of novel azanonaboranes as potential agents for boron neutron capture therapy

摘要

A number of (hydroxyalkylamine)-N-(aminoalkyl)azanonaborane(ll) derivatives have been synthesized to provide azanonaboranes with different hydrophilic functional groups for use in the treatment of cancer by boron neutron capture therapy (BNCT).The exo-diamine group of (aminoalkylamine)-N-(aminoalkyl)azanonaborane(ll){H_2N(CH_2)_mH_2NB_8H_(11)NH(CH_2)_mNH_2,where m = 4-6} can be substituted by amino alcohol ligands {HO(CH_2)_nNH_2,where n = 3 and 4} to give azanonaboranes containing free amino and hydroxy groups:(3-hydroxypropylamine)-N-(aminobutyl)azanonaborane(ll) {HO(CH_2)_3H_2NB_8H_(11)NH(CH_2)_4NH_2},1;(4-hydroxybutylamine)-N-(aminobutyl)azanonaborane(ll) {HO(CH_2)_4H_2NB_8H_(11)NH(CH_2)_4NH_2},2;(3-hydroxypropylamine)-N-(aminopentyl)azanonaborane(ll) {HO(CH_2)_3H_2NB_8H_(11)NH(CH_2)_5NH_2},3;(4-hydroxypropylamine)-N-(aminopentyl)azanonaborane(ll) {HO(CH_2)_4H_2NB_8H_(11)NH(CH_2)_5NH_2),4;(3-hydroxypropylamine)-N-(aminohexyl)azanonaborane(ll) {HO(CH_2)_3H_2NB_8H_(11)NH(CH_2)_6NH_2},5.The in vitro toxicity test using Chinese hamster-V79 cells showed that compounds 1-3 were less toxic (LD_(50) value of approx 2.3,1.7 and 1.4 mM,respectively) than spermine and spermidine (LD_(50) value of approx 0.88 and 0.66 mM,respectively).In vivo distribution experiments of these compounds in Lewis lung carcinoma and B16 melanoma tumor-bearing mice showed that boron can be found in tumor tissue.The compounds prepared can be considered as a new class of boron containing polyamine compounds that may be useful for boron neutron capture therapy of tumors.