Purine and 8-substituted purine arabinofuranosyl and ribofuranosyl nucleoside derivatives as potential inducers of the differentiation of the Friend erythroleukemia.
Several antimetabolites have been demonstrated to have the capacity to initiate differentiation in vitro of a variety of leukemic cell lines. To explore the structural requirements for this activity, a series of purine and 8-substituted purine arabinofuranosyl and ribofuranosyl nucleoside derivatives were synthesized and tested as inducers of the differentiation of Friend murine erythroleukemia cells. 9-(beta-D-Arabinofuranosyl)hypoxanthine and 6-(hydroxyamino)-9-(beta-D-arabinofuranosyl)purine were effective inducers of maturation, producing 82% and 74% benzidine-positive cells, a measure of the number of cells synthesizing hemoglobin. 6-Mercapto-9-(beta-D-ribofuranosyl)purine and 6-(methylmercapto)-9-(beta-D-ribofuranosyl)purine and their corresponding beta-D-arabinofuranosyl derivatives were also effective initiators of maturation, causing approximately 50% of the cell population to assume a differentiated phenotype.
D000818:Animals; D000963:Antimetabolites / Q000138:chemical synthesis / Q000494:pharmacology; D001087:Arabinonucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D005622:Friend murine leukemia virus; D006410:Hematopoiesis / Q000187:drug effects; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D051379:Mice; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D012263:Ribonucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000963:Antimetabolites; D001087:Arabinonucleosides; D011684:Purine Nucleosides; D012263:Ribonucleosides