Journal of Medicinal Chemistry p. 405 - 409 (1987)
Update date:2022-08-04
Topics:
Haces, Alberto
Breitman, Theodore R.
Driscoll, John S.
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.
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