Thionamides and analogues: a reapraisal of antithyroid and thyroid carcinogenic effects.
As commonly depicted, in the thione form, thionamides (including thiourea and its derivatives) bear little resemblance to thyroid hormone. However, if placed in the thiol resonance form, these molecules are noted to structurally mimic the end of the tyrosine molecule (the precursor of thyroid hormone). Alternatively, tyrosine written in the -one configuration resembles the thionamides. This permits a better appreciation of why the thionamides may themselves be iodinated by thyroid peroxidase in some cases, and under other circumstances induce changes in the enzyme. The thiol resonant form can be written for naturally occurring goitrin, and for thiobarbituric acids with antithyroid activity. An hydroxyl resonant configuration can be drawn for the antithyroid compound 3-hydroxy-4-pyridone. Tetramethylthiourea is a thyroid carcinogen in rats. The compound can not be readily placed in the thiol resonant configuration; it also contains 2 methyl groups at both ends of the molecule. The hair dye 2,4-diaminoanisole sulfate induces thyroid neoplasms in rats. A similarity is pointed out both to tyrosine an to lower potency antithyroid aminobenzenes (described by Astwood and coworkers). Pyrazole, known to produce thyroid necrosis, is seen to have a distinct resemblance to the opposite end of several of these compounds.
D013956:Antithyroid Agents; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D011725:Pyridines; D013329:Structure-Activity Relationship; D013858:Thiobarbiturates; D013871:Thiones; D013890:Thiourea; D013963:Thyroid Hormones; D013964:Thyroid Neoplasms / Q000139:chemically induced*; D014443:Tyrosine
D013956:Antithyroid Agents; D002273:Carcinogens; D011725:Pyridines; D013858:Thiobarbiturates; D013871:Thiones; D013963:Thyroid Hormones; D014443:Tyrosine; D013890:Thiourea