Beta-substituted cysteines as sequestering agents for ethanol-derived acetaldehyde in vivo.
A series of beta-mono- and beta,beta-disubstituted cysteines were evaluated in rats as sequestering agents for metabolically generated acetaldehyde (AcH) during the oxidation of ethanol in vivo and compared against D-(-)-penicillamine. Both threo- (5) and erythro-beta-phenyl-DL-cysteine (6) reduced ethanol-derived blood AcH by ca. 40% and 60%, respectively, whereas the corresponding beta-methyl-DL-cysteines (3 and 4) and the alpha-substituted alpha-methyl-DL-cysteine (8) had no effect. beta,beta-Tetramethylene-DL-cysteine (7), however, was as effective as D-(-)-penicillamine in sequestering AcH in vivo, reducing blood AcH after ethanol to 20% of maximal values. Thus, bulky beta-substitution or, better, beta,beta-disubstitution on cysteine is required for such activity. 14C-Labeled 2(RS),5,5-trimethylthiazolidine-4(S)-carboxylic acid (1) prepared by the condensation of D-(-)-penicillamine with [1,2-14C]acetaldehyde was found to be relatively stable in vivo, giving rise to less than 6% 14CO2 excretion in the expired air and the recovery of 65.5% of the administered dose in the urine as unchanged 1.
D000079:Acetaldehyde / Q000097:blood*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003484:Cyanamide / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D000431:Ethanol / Q000097:blood*; D008297:Male; D010084:Oxidation-Reduction; D010396:Penicillamine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000431:Ethanol; D003484:Cyanamide; D010396:Penicillamine; D000079:Acetaldehyde; D003545:Cysteine; D004221:Disulfiram