Bs. Burnham et al., THE CYTOTOXICITY OF 3'-AMINOCYANOBORANE-2', 3'-DIDEOXPYRIMIDINES IN MURINE AND HUMAN TISSUE-CULTURED CELL-LINES, Anticancer research, 15(3), 1995, pp. 951-958
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.