THE CYTOTOXICITY OF 3'-AMINOCYANOBORANE-2', 3'-DIDEOXPYRIMIDINES IN MURINE AND HUMAN TISSUE-CULTURED CELL-LINES

3'-Aminocyanoborane-2': 3'-dideoxythymidine(VIIIa) and 3'-aminocyanobo rane-2',: 3'-dideoxyuridine(VIIIb) were successfully synthesized. The thymidine derivative(VIIIa) was shown to be a potent cytotoxic agent i n murine and selected human suspended and solid armor cell lines. Comp ound VIIIa inhibited L-1210 leukemia DNA and RNA synthesis with the pr otein synthesis requiring a higher concentration of drug for inhibitio n within 60 min. The purine pathway appeared to be the major target of Compound VIIIa with inhibition of IMP dehydrogenase and dihydrofolate reductase activities. The compound affected metabolic enzyme activiti es in the pyrimidine pathway as well as the nucleoside kinase activiti es. The DNA molecule did not appear to be target of the 3'-aminocyanob orane-2', 3'-dideoxythymidine (VIIIa), in that there was no change in ct-DNA viscosity, thermal denaturation ol absorption of nucleosides of DNA nor was there any L-1210 DNA strand scission ol inhibition of L-1 210 DNA topoisomerase II activity when compound VIIIa was incubated at 100 mu M.