Synthesis and biological evaluation of boron-containing polyamines as potential agents for neutron capture therapy of brain tumors

New boron-containing spermidine/spermine (SPD/SPM) analogues have been synt hesized: N-5[4-(2-aminoethyl-o-carboranyl)butyl] and N-5-{4-[(2,3-dihydroxy propyl)-o-carboranyl]} SPD/ SPM derivatives (ASPD-5, ASPM-5, DHSPM-5, and D HSPM-5) as well as N-5-{[4-(dihydroxyboryl)phenyl]methyl}spermidine (BBSPD- 5). These boronated polyamines retain their ability to displace ethidium br omide from calf thymus DNA and are rapidly taken up in vitro by F98 rat gli oma cells. The in vitro toxicities of ASPD-5, ASPM-5, DHSPD-5, and DHSPM-5 are lower than those previously reported for N-5-[4-(o-carboranyl)butyl] SP D/SPM derivatives (SPD-5 and SPM-B) but similar to those of native SPD and SPM. Very low toxicity was also observed for BBSPD-5. In vivo studies of AS PD-5 and BBSPD-5 were performed in mice bearing intracerebral implants of t he GL261 glioma and subcutaneous implants of the B16 melanoma. The biodistr ibution data found in both tumor models suggest that the polyamines synthes ized to date do not appear to be suitable boron agents for BNCT.