Structural requirements for the sequestration of metabolically generated acetaldehyde

Of a series of polyfunctional compounds containing amino, hydroxyl, or mercapto groups in conjunction with the carboxyl group, only the 1,2- or 1,3-disubstituted aminothiols, namely, D-(-)-penicillamine (1), L-cysteine (2), L-cysteinyl-L-valine (3), mercaptoethylglycine (4), and DL-homocysteine (12), showed any propensity to sequester acetaldehyde (AcH) when tested in vitro in a buffered system at pH 7.5. In vivo, however, only D-(-)-penicillamine (1) was effective in lowering ethanol-derived blood AcH in rats that had been treated with disulfiram and ethanol. These results suggest that, in addition to the functionality in the molecule, pharmacokinetic and metabolic factors must also be considered when designing AcH-sequestering agents for use in vivo.