Inhibition of nucleic acids and protein synthesis by deazaadenosine derivatives: a study on structure-activity relationships.
The effect of four deaza-analogues of adenosine on the synthesis of nucleic acids and proteins was investigated in monkey kidney cell line Vero. Cells in exponential growth phase were exposed for two hours to 1, 3 or 10 microM concentrations of 1-deazaadenosine (c1Ado), 3-deazaadenosine (c3Ado), 7-deazaadenosine (c7Ado) or 1,3-dideazaadenosine (c1,3Ado) in a serum free medium; the rate of macromolecules synthesis was estimated after one hour pulse treatment with radiolabelled precursors. At the concentrations used, c1Ado and c3Ado produced no or very little change in the rate of macromolecules synthesis: c1Ado slightly increased RNA synthesis whereas c3Ado was a weak inhibitor of DNA synthesis. Conversely, c7Ado was a potent inhibitor of macromolecules synthesis. Two hours of drug exposure at a concentration of 10 microM, resulted in a 40-50% inhibition in DNA, RNA and protein synthesis rates. c1,3Ado did not significantly affect RNA or protein metabolism but produced a dramatic increase in DNA synthesis. No DNA breaks could be detected in cells exposed to the agents tested in this study.
Cantoni
O
O
Sestili
P
P
Balduini
W
W
Cristalli
G
G
Grifantini
M
M
Cattabeni
F
F
D000818:Animals; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D000882:Haplorhini; D006861:Hydrogen Peroxide / Q000378:metabolism; D007668:Kidney; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis*; D012263:Ribonucleosides / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014372:Tubercidin / Q000031:analogs & derivatives / Q000494:pharmacology*
D012263:Ribonucleosides; C018258:3-deazaadenosine; C048086:1-deazaadenosine; C048085:1,3-dideazaadenosine; D012313:RNA; D004247:DNA; D006861:Hydrogen Peroxide; D014372:Tubercidin