An N-hydroxylated derivative of cyanamide that inhibits yeast aldehyde dehydrogenase

A stable, N,O-dibenzoyl derivative (DBHC) of N-hydroxycyanamide, the latter the postulated bioactivation product of the alcohol deterrent agent, cyanamide, has been synthesized. DBHC was an effective inhibitor of yeast aldehyde dehydrogenase (AIDH) in vitro and inhibited this enzyme in a concentration-dependent manner with an IC50 of 25 microM. Hydrolysis of the benzoate moiety of DBHC with dilute NaOH gave rise to the formation of nitroxyl (HN = O), detected by gas chromatography as nitrous oxide (N2O), the end-product of nitroxyl dimerization and disproportionation. It is postulated that the nitroxyl liberated by esterase action on DBHC by yeast AIDH may be the reactive species that inhibits AIDH.