Boron substituted deoxyribonucleosides as cytotoxic agents
Hall, I.H.; Elkins, A.; Sood, A.; Tomasz, J.; SpielVogel, B.F.
Anticancer Research 16(6b): 3709-3714
1996
ISSN/ISBN: 0250-7005 PMID: 9042245 Document Number: 465145
Base substituted boronated nucleosides and phosphate modified nucleotides were examined for their cytotoxic activity in both murine and human tissue cultured cancer cells. These derivatives demonstrated better activity against the growth of single cell suspensions than solid cell tumor cell growth. A detailed mode of action study showed that 2'deoxyriboadenosine-N-7-cyanoborane 6 suppressed Tmolt-3 DNA synthesis preferentially with the major target of the agent being the purine de novo pathway. The activities of one of the regulatory enzymes of the pathway were reduced by the agents, i.e., PRPP-amido transferase. Other sites in the cell which were moderately affected by the agent were nucleoside kinase activities, DNA polymerase alpha. and dihydrofolate reductase activities. The DNA molecule itself did not appear to be a target of the compound.