Cytotoxicity of ribo-and arabinoside boron nucleosides in tissue culture cells

Ribose and arabinoside boron nucleoside derivatives were shown to be potent cytotoxic agents in murine and human suspended and solid tumor cell lines. The arabinoside derivative inhibited DNA and RNA synthesis with the protein synthesis requiring a higher concentration of drug for inhibition within 60 min. The purine pathway appeared to be the major target of the arabinoside 1 with inhibition of PRPP amido transferase and IMP dehydrogenase activities. Blockage of this pathway afforded reductions of deoxyadenosine and deoxyguanosine nucleotide pools. The DNA template did not appear to be target of the arabinoside 1, in that there was no change in DNA viscosity, thermal denaturation or absorption of nucleosides of DNA. However, compound 1 when incubated with L-1210 cells for 24 hr. showed a slight shift of the DNA in the gradient and moderate inhibition of ct-DNA topoisomerase II was demonstrated by 1 in vitro.