Chemical differentiating agents. Differentiation of HL-60 cells by hexamethylenebis[acetamide] analogues.
Hexamethylenebis[acetamide] (HMBA) is an agent in clinical trial that induces differentiation of certain types of tumor cells to nonmalignant phenotypes. In an attempt to discover a more potent compound, a number of bis-functionalized amides, imides, and hydrazine derivatives of HMBA were prepared and evaluated in vitro with the HL-60 human promyelocytic leukemia cell line. Among the compounds evaluated, the 5,5-dimethylhydantoin derivative is almost 10 times more potent than HMBA in inducing differentiation. The bis-imide, diacetyl-HMBA, is both more potent and effective than its parent compound. Six of the 16 compounds evaluated cause at least 20% differentiation. An inverse relationship between the degree of differentiation and the percentage of viable cells is described for HMBA and its analogues.
D000081:Acetamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013329:Structure-Activity Relationship
D000081:Acetamides; D007202:Indicators and Reagents; C014026:hexamethylene bisacetamide