Nucleosides. 1. 9-(3'-Alkyl-3'-deoxy-beta-D-ribofuranosyl)adenines as lipophilic analogues of cordycepin. Synthesis and preliminary biological studies.
A series of lipophilic 9-(3'-alkyl-3'-deoxy-beta-D-ribofuranosyl)adenines of increasing chain length was synthesized from the corresponding branched sugars via titanium chloride catalyzed ribosylation of chloromercuri-6-benzamidopurine. Enhanced growth inhibitory activity was observed against (CCRF-CEM human lymphoblastic leukemia cells in culture as the length of the alkyl side chain in the sugar and the resultant lipophilic character of the nucleoside were increased. Experiments involving incorporation of radiolabeled uridine, thymidine, and leucine revealed that in contrast to cordycepin (1) the 3'-n-butyl and 3'-n-hexyl analogues 5 and 6 markedly inhibit not only RNA synthesis but DNA and protein synthesis as well.
D000818:Animals; D000962:Antimalarials; D000970:Antineoplastic Agents; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D003839:Deoxyadenosines / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007945:Leukemia, Lymphoid / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D014176:Protein Biosynthesis; D012313:RNA / Q000096:biosynthesis; D013329:Structure-Activity Relationship
D000962:Antimalarials; D000970:Antineoplastic Agents; D003839:Deoxyadenosines; D012313:RNA; D004247:DNA