The development of carboranyl nucleic acid precursors for use in neutron capture therapy of tumors

The synthesis of a carboranyl nucleic a cid precursor 2'-0-(0- carboran-1-yl rnethyl)uridine, 1, and a carboranyl n ucleotide, 8, is described. Significantly greater incorporation and persistence of 1 in F9g glioma cells, compared with the clinically used Na2812HllSH is observed. The development of boron compounds for the treatment of cancer by boron neutron capture therapy (BNCT) is based upon the nuclear fission of nonradioactive boron-10 atoms by thermal neutrons, generating high linear energy transfer (LET) particles (1). These have a destruc- tive range of approximately 10 um. The biological effectivenes of BNCT is greater if boron compounds are localized intracellularly vis-a-vis on cell membrane or in extracellular spaces. capture reaction were to occur in the cell nucleus rather than in the cytoplasm (2). closer proximity of the boron compound to the tumor cell nucleus, therefore, t he g reater its radiobiological effect. question? One of the early approaches was the attempted synthesis of boron heterocycles, which may be viewed as analogues of the p urine and pyrimidine bases of the naturally- occurring nucleic acids (3-7). Many of these, however, were hydrolytically unstable and/or failed to mimic the bases as measured by cellular incorporation. One structure which more closely resembled these precursors was 5-dihydroxyboryl uracil