The structural specificity of sulfanilamide-like compounds as inhibitors of the invitro conversion of inorganic iodide to thyroxine and diiodotyrosine by thyroid tissue.

By means of radioactive iodine it was demonstrated in this laboratory that surviving slices of thyroid tissue can incorporate inorganic iodide into diiodotyrosine and thyroxine (1). When 300 mg. of thyroid slices were incubated for 2 hours in a Ringer’s medium containing radioactive inorganic iodide, as much as 60 per cent of the labeled iodine was organically bound, about 50 per cent as diiodotyrosine and about 10 per cent as thyroxine. This in vitro reaction has provided a new and useful approach to the study of the biosynthesis of thyroxine. Thus, it was used to determine the mechanism by which the prolonged administration of the sulfonamides produces an enlargement of the thyroid gland, a hypertrophy t’hat is characterized by hyperplasia and a loss of colloid. It was shown that at concentrations of 10e3 M sulfanilamide, sulfapyridine, sulfathiazole, and sulfaguanidine depressed the synthesis of radiodiiodotyrosine and radiothyroxine (2). These compounds therefore act directly on the conversion of inorganic iodide to diiodotyrosine and thyroxine by thyroid tissue. p-Aminobenzoic acid and p-aminophenylacetic acid, because of their structural similarity to the sulfonamides, were also tested and found to be inhibitors (3). In view of the importance of these findings to an understanding of the mechanism of biosynthesis of thyroxine, it became of interest to determine the structural part of the above molecules essential for their inhibitory action. Hence in the present investigation forty compounds structurally relat,ed to either sulfanilamide of p-aminobenzoic acid have been tested for their effects on in vitro formation of thyroxine and diiodotyrosine.