BORON-CONTAINING POLYAMINES AS DNA TARGETING AGENTS FOR NEUTRON-CAPTURE THERAPY OF BRAIN-TUMORS - SYNTHESIS AND BIOLOGICAL EVALUATION

Three series of new boron-containing spermidine/spermine (SPD/SPM) ana logues have been synthesized: N1(-) and N-5-(4-carboranylbutyl) SPD/SP M derivatives (SPD-1, SPD-5, SPM-1, SPM-5); N-1,N-10-diethyl-N-5-(4-ca rboranylbutyl)spe (DESPD-5), N-1,N-14-diethyl-N-5-(4-carboranylbutyl)s permine (DESPM-5); and N-5,N-10-bis(4-carboranylbutyl)spermine (SPM-5, 10). In vitro studies using rat F98 glioma cells have shown that these polyamines retain the ability to displace ethidium bromide from calf thymus DNA and are rapidly taken up by F98 glioma cells. However, thei r cytotoxicities, especially those with terminal N-substituted (SPD-1, SPM-1) boron compounds, are greater than those of SPD/SPM. Neverthele ss, the groundwork has been created for a new class of boron-containin g compounds that maybe useful for boron neutron capture therapy of tum ors.