STRUCTURE-ACTIVITY RELATIONSHIPS IN 5-SUBSTITUTED 3-AMINO-1,2,4-TRIAZOLES-INDUCED GOITERS IN RATS

概要

論文の詳細を見る
The goitrogenic actions of 5-substituted 3-amino-l, 2, 4-triazoles, 3-amino-5-mercapto-l, 2, 4-triazole (AMTZ), 3-amino-1, 2, 4-triazole-5-carboxylic acid (ATZC), 3, 5-diamino-l, 2, 4-triazole (DTZ), 3-amino-5-methylthio-l, 2, 4-triazole (AMTTZ), and 3-amino-1, 2, 4- triazole (ATZ) were compared in rats. ATZ, AMTZ, ATZC, and DTZ inhibited the thyroid peroxidase (TPO)-catalyzed oxidation of guaiacol in vitro, exhibiting the order of antithyroid activity ATZ>AMTZ>ATZC>DTZ. In in vivo experiments, ATZ, ATZC, or AMTZ inhibited TPO activity, and induced goiter accompanied by decrease in serum thyroid hormone and increase in serum thyroid-stimulating hormone in rats. These antithyroid activities were shown in order of ATZ>ATZC>AMTZ. The TPO inhibitory action of ATZC in vivo was weaker than that of AMTZ, but it was more persistent than AMTZ. The anti-TPO action of DTZ disappeared in vivo, and AMTTZ showed no effects in vitro and in vivo. These results show that ATZC, AMTZ, and DTZ potentially have the anti-TPO activity like as ATZ and the 5-position site of ATZ would have a very important meaning to determine the antithyroid action of ATZ. In addition, the results strongly suggest that the anti-thyroid action depends on the substitute but not on the parental compound.
日本毒性病理学会の論文