Inducers of erythroleukemic differentiation. Relationship of structure to activity among planar-polar compounds.
Hexamethylenebisacetamide is a potent inducer of erythroid differentiation in murine erythroleukemia cells. A series of chemical compounds structurally related to hexamethylenebisacetamide were tested for inducing activity including polymethylene chains terminally substituted with various combinations of carboxylate, amino, amide, or sulfoxide groups. Effective "dimerization" of dimethyl sulfoxide through a linear polymethylene chain increases its inducing activity by a magnitude similar to that observed when N-methylacetamide is effectively dimerized in such a manner. It was found that all potent inducing agents possess both a hydrophilic and hydrophobic portion of the molecule, as well as a planar portion. All are Lewis bases, possessing a free electron pair available for hydrogen bonding. The polymethylene chain joining functional groups must be flexible and must be 5 to 6 carbon atoms in length to achieve maximal activity. Introduction of triple or double (cis or trans) bonds into the polymethylene chain does not alter activity.
D000081:Acetamides / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004915:Leukemia, Erythroblastic, Acute / Q000503:physiopathology*; D013329:Structure-Activity Relationship
D000081:Acetamides; D000577:Amides; D002264:Carboxylic Acids; D003998:Dicarboxylic Acids; D004121:Dimethyl Sulfoxide