A new group of potent inducers of differentiation in murine erythroleukemia cells.
This report identifies a group of compounds, polymethylene bisacetamides (acetylated diamines), which are potent inducers of erythroid differentiation in murine erythroleukemia cells. A known inducing agent, N-methylacetamide, was dimerized through varying numbers of methylenes in an attempt to increase the local effective concentration at adjacent target sites. The simple dimer was no more effective than N-methylacetamide alone; introduction of five to eight methylenes between acetamide groups substantially increased the effectiveness of these compounds. The hexamethylene bisacetamide was active between 0.5 mM and 5 mM; the percentage of cells induced and the rate at which they were recruited to differentiation was dependent upon the concentration of inducer within this range. At 5 mM hexamethylene bisacetamide essentially the entire population (greater than 99%) was induced to a pathway of erythroid differentiation which was greater differentiation of the cultured cells than with any inducer yet tested.
D000081:Acetamides / Q000494:pharmacology*; D001560:Benzidines / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006454:Hemoglobins / Q000096:biosynthesis; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism / Q000473:pathology*; D013329:Structure-Activity Relationship
D000081:Acetamides; D001560:Benzidines; D006454:Hemoglobins; D004121:Dimethyl Sulfoxide