| Description |
Glutathione is essential in preventing hepatotoxicity. However, it can be depleted as in the case of acetaminophen overdose. The production of glutathion e increases in the presence of cysteine. The potential for toxicity of cysteine is overcome by the administration of cysteine prodrugs in the form of 2-substituted thiazolidines. The 2-substituted cysteine ethyl ester derivatives are essentially pro-prodrugs. They were synthesized in the hope of increasing lipophilicity and thus decreasing excretion through the kidneys. Intracellular esteras es are expected to cleave the ester bond releasing the cysteine prodrug which would further dissociate to release cysteine. These cysteine prodrugs dissociate to release the free amino acid and the aldehyde which corresponds to the substituent at the 2-position of the thiazolidine. Upon studying the dissociation of the 2-substituted thiazolidine esters, peaks appear which correspond to methyl and ethyl alcohols. The appearance the putative alcohol peaks is seen in all the derivatives regardless of the nature of the substituent at the 2-position. In no case was the cysteine ester observed; however, there were indications that the thiazolidine ring was opening to release the aldehyde of the 2-substituent. Clearly the acid and ester derivatives exhibit very different dissociation characteristics although the exact reasons for those differences remain to be elucidated. |
