Abstract：
:A series of purine nucleoside and dialdehyde analogues was studied to determine their potency as inhibitors of C-1300 murine neuroblastoma cell growth in tissue culture. Tumor cells were incubated with each analogue for 72 h, and the number of viable cells was determined at 24, 48, and 72 h. Dose-response curves were generated (concentration range, 10(-8) to 10(-3) M), and the drug concentration producing 50% inhibition of cell growth was calculated for each analogue. The 50% inhibitory concentrations, in ascending order of potency, were as follows: adenosine (inactive); S-adenosylhomocysteine (inactive); methylfuryladenine (5.6 X 10(-1)M); adenosine 5'-carboxylic acid (2.0 X 10(-1)M); 5'-chloro, 5'-deoxy-ara-adenosine (3.0 X 10(-2)M); sinefungin (1.7 X 10(-3) M); 5'-deoxyadenosine (2.2 X 10(-4)M); 5'-chloro, 5'-deoxyadenosine (2.1 X 10(-4)M); 3',5'-dichloro, 2',3',5'-trideoxyadenosine (1.3 X 10(-4)M); 3-deazaadenosine (5.6 X 10(-5)M); and adenosine dialdehyde (1.5 X 10(-6)M). Oxidation of the pentose to a dialdehyde increased, whereas reduction of the dialdehyde or substitution of adenine with either hypoxanthine, guanine, uracil, or cytosine decreased the inhibitory potency. The analogues 4',5'-anhydroadenosine dialdehyde and 5'-deoxyadenosine dialdehyde, which cannot be phosphorylated at the 5' position, had 50% inhibitory concentrations of 9.1 X 10(-6) and 7.6 X 10(-6)M, respectively. These data suggest that the inhibitory action and potency of nucleoside dialdehydes on neuroblastoma growth are independent of their capacity to undergo a kinase-mediated phosphorylation at the 5' position.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Mirkin BL,O'Dea RF,Hogenkamp HPsubject
Has Abstractpub_date
1987-07-15 00:00:00pages
3650-5issue
14eissn
0008-5472issn
1538-7445journal_volume
47pub_type
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