EVALUATION OF IN-VITRO CYTOTOXICITY OF CARBORANYL AMINO-ACIDS, THEIR CHEMICAL PRECURSORS AND NIDO CARBORANYL AMINO-ACIDS FOR BORON NEUTRON-CAPTURE THERAPY

The purpose of the present study was to define the in vitro cellular t oxicity of three carborane-containing amino acids. p-(o-carboran-yl)-p henylalanine (CBPA), O-(o-carboran-1-ylmethyl)-tyrosine (CBT), and o-c arboranylalanine (CBA), which are analogues of phenylalanine, tyrosine , and alanine respectively. In addition, two of their chemical precurs ors: CBACN (B10H11C2-CH2CHNH2CN) and CBTCN (B10H11C2CH2OC6H4CH2CHNH2CN ) and nido CBA were evaluated for their toxicity on human MRA 27 melan oma cells. Hydroxypropyl-beta-cyclodextrin (beta-CD) initially was use d to solubilize all the compounds except nido CBA in the toxicity assa ys Cells were incubated with the test compounds at varying concentrati ons for 24 hrs, following which the proliferative activity of survivin g cells was determined by pulsing with tritiated thymidine ([H-3]-TdR) for an additional 18 hrs. CBT at a concentration of 280 mu g/ml was n on-toxic when solubilized with beta-CD. CBA at a concentration of 350 mu g/ml was non-toxic wizen solubilized with beta-CD, but when solubil ized with DMSO produced a 50% reduction in uptake of [H-3]-TdR at a co ncentration of 75 mu g/ml. CBPA, solubilized with beta-CD, was nontoxi c at a concentration of 400 mu g/ml, while CBTCN and CBACN at concentr ations of 50 mu/ml respectively, were both toxic, even when solubilize d with beta-CD. Nido CBA at a concentration of 400 mu g/ml in medium w as nontoxic. Although the toxicity of these boron compounds precludes their use as capture agents for Neutron Capture Therapy, they may have some potential for cytoreductive chemotherapy of cancer, and further evaluation may be warranted.