Chelation in metal intoxication. XIX. alpha-Mercapto-beta-aryl acrylic acid as antidotes to nickel and lead toxicity.

In view of the reported effectiveness of alpha-mercapto-beta-(2-furyl) acrylic acid (MFA) as an effective antidote to inorganic mercury toxicity, some alpha-mercapto-beta-aryl acrylic acids were synthesized and examined for their efficacy in counteracting nickel and lead intoxication in rats. alpha-mercapto-beta-(3,4-dimethoxyphenyl)acrylic acid (MDA) was most effective and other compounds were less but about equally effective in enhancing urinary excretion and in reducing tissue concentration of Ni. MDA was the only compound to remove Ni from the brain. MFA was also more effective than other structurally related compounds in enhancing urinary and faecal excretion and in lowering body burden of Pb. All the compounds significantly reduced the inhibition of the activity of blood delta-aminolevulinic acid dehydratase (delta-ALA-D) and increase in the urinary excretion of delta-aminolevulinic acid (delta-ALA) caused by Pb. The results do not show any relationship between the nature of the substitution at the beta-position of alpha-mercapto acrylic acids and their ability to reduce the concentration and the toxic effects of the two metals. However, these thiol chelating agents appear promising as antidotes to Ni and Pb poisoning.