Chemical differentiating agents. Differentiation of HL-60 cells by hexamethylenebis[acetamide] analogues.

Abstract

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.

• Authors: A Haces, T R Breitman, J S Driscoll
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 30 Issue 2 Pg. 405-9 (Feb 1987) ISSN: 0022-2623 [Print] United States
• PMID: 3806621 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Acetamides
• Indicators and Reagents
• hexamethylene bisacetamide

Topics

• Acetamides (chemical synthesis, pharmacology)
• Cell Differentiation (drug effects)
• Cell Line
• Humans
• Indicators and Reagents
• Magnetic Resonance Spectroscopy
• Mass Spectrometry
• Structure-Activity Relationship