Comparison of the effects on cultured L1210 leukemia cells of the ribosyl, 2'-deoxyribosyl, and xylosyl homologs of tubercidin and adenosine alone or in combination with 2'-deoxycoformycin.
The biologic effects of a series of sugar-substituted analogs of tubercidin were evaluated and compared with the effects of the homologous series of adenosine analogs in combination with 2'-deoxycoformycin. The greatest cytotoxicity against cultured mouse L1210 leukemia cells was exhibited by tubercidin and by 3'-deoxyadenosine or xylosyladenine in combination with 2'-deoxycoformycin. Somewhat less active were xylotubercidin and the combination of arabinosyladenine (araA) plus 2'-deoxycoformycin. The arabinosyl and 2'- and 3'-deoxyribosyl derivatives of tubercidin were relatively ineffective in their ability to inhibit proliferation of L1210 cells. The major biochemical effects of the most active agents were inhibition of RNA synthesis (3'-deoxyadenosine and xylosyladenine) and depletion of cellular ATP plus general inhibition of macromolecular synthesis (tubercidin). The in vitro activities of xylosyladenine and 3'-deoxyadenosine (in combination with 2'-deoxycoformycin) and xylotubercidin (as a single agent) were greater than or equivalent to that of araA (in combination with 2'-deoxycoformycin).
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009711:Nucleotides / Q000378:metabolism; D015649:Pentostatin; D012263:Ribonucleosides / Q000494:pharmacology*; D014372:Tubercidin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D009711:Nucleotides; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; D000241:Adenosine; D014372:Tubercidin