Purine and 8-Substituted Purine Arabinofuranosyl and Ribofuranosyl Nucleoside Derivatives as Potential Inducers of the Differentiation of the Friend Erythroleuukemia

Article abstract of DOI:10.1021/jm00148a018

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-(β-D-Arabinofuranosyl)hypoxanthine and 6-(hydroxyamino)-9-(β-D-arabinofuranosyl)purine were effective inducers of maturation, producing 82percent and 74percent benzidine-positive cells, a measure of the number of cells synthesizing hemoglobin. 6-Mercapto-9-(β-D-ribofuranosyl)purine and 6-(methylmercapto)-9-(β-D-ribofuranosyl)purine and their corresponding β-D-arabinofuranosyl derivatives were also effective initiators of maturation, causing approximately 50percent of the cell population to assume a differentiated phenotype.