NEW CARBORANE-BASED COMPOUNDS FOR BORON NEUTRON-CAPTURE THERAPY - BINDING AND TOXICITY OF ANC-1, DAC-1 AND B-ET-11-OME IN CULTURED HUMAN GLIOMA AND MOUSE MELANOMA-CELLS

The toxicity and binding of the three new carborane based compounds: 2 (1,2-dicarba-closo-dodecaborane (-yl-methoxy)-2-(3-amino-propyl))-1,3 -propanediol, called DAC-1; 7-(3-amino-propyl)-7,8-dicarba-nido-undeca rborate (-1) called ANC-1; and rboranyl)-nonyl-2-methyl-glycero-3-phos phocholine, called B-Et-11-OMe, were analyzed with cultured human glio ma cells, U-343MGa, and mouse melanoma cells, B16, as biological model s. The previously developed compound di-sodium undecahydro-mercapto-cl oso-dodecarborate (BSH), which is tested for therapy of malignant glio mas, was analyzed for comparison. In the toxicity tests the cells were exposed to the substances at cell culture medium concentrations in th e range 0-50 ppm boron for 1 or 20 h and thereafter analyzed regarding growth. Growth-disturbing effects were seen for the two compounds DAC -1 and B-Et-11-OMe at the concentrations corresponding to 15 and 50 pp m boron, respectively. The compounds ANC-1 and BSH showed no growth-di sturbing effects at the tested concentrations. In the binding tests, t he cells were incubated for 20 h at about the highest compound concent rations that did not cause growth disturbances. The boron content in t he cells was then determined by inductively coupled plasma-atomic emis sion spectrometry (ICP-AES) and in some cases ICP-mass spectrometry (I CP-MS). The most extensive binding was seen for DAC-1 and B-Et-11-OMe, which accumulated boron to about 100 and 60 times, respectively, comp ared with the concentration in the culture medium. The compound ANC-1 also accumulated boron in the cells but the boron could be easily wash ed out indicating no or only a weak binding. BSH did not accumulate. F urther analysis should be made regarding biological properties such as intracellular compartmentalization, metabolic interference and tumor specificity of the compounds DAC-1 and B-Et-11-OMe.