Reducing property of some slow acting antirheumatic drugs

Many slow acting antirheumatic drugs and several other drugs without antirheumatic activity possess a potential thiol function, i.e., a free SH group or one that is generated by hydrolysis. Since drugs with effective SH activity may react with intracellular disulfides, we evaluated their reducing properties by measuring their redox potential and their ability to react with glutathione, the most prevalent intracellular thiol, and dithiobis (nitrobenzoic acid), a specific reactant for thiols. Drugs containing aromatic thiols are poor reducers and are generally devoid of antirheumatic activity. Antirheumatic drugs, such as D-penicillamine, levamisole, gold salts, thiopronine and captopril, are potential aliphatic thiols with strong reducing properties. These different antirheumatic drugs may therefore operate by a common mechanism through an altered cellular redox equilibrium and sulfide-disulfide exchanges.