Cordycepin analog of (A2'p)2A: evidence that it functions as a prodrug of cordycepin.
The effect of the cordycepin trimer analog of (A2'p)2A on cell growth, cell viability and nucleic acid synthesis was assessed in human colon carcinoma cell line HT-29 in vitro. The cordycepin analog, (3'dA2'p)2(3)'dA reduced 24 hr cell growth by 50% at 10(-4)M and decreased cell viability by 98% under these conditions. The cytotoxicity and inhibitory effects of (3'dA2'p)2(3)'dA on DNA and RNA synthesis were potentiated 5-10-fold by the presence of the adenosine deaminase inhibitor, 2'-deoxycoformycin, and closely resembled those of the parent drug, cordycepin. Chromatographic analyses of the stability of (3'dA2'p)2(3)'dA in the tissue culture medium indicated that it was hydrolyzed to the dimer and monomer forms with a half life of approximately 2 hr. No intact (3'dA2'p)2(3)'dA was detectable intracellularly, but large concentrations of cordycepin nucleotide metabolites were formed, particularly in the presence of 2'-deoxycoformycin.
D000230:Adenocarcinoma; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms; D004261:DNA Replication / Q000187:drug effects*; D003839:Deoxyadenosines / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D007700:Kinetics; D014158:Transcription, Genetic / Q000187:drug effects*
D003839:Deoxyadenosines