Sites of action of 2-thiazoline-2-thiol on biogenesis of thyroid hormones.
2-Thiazoline-2-thiol is an antithyroid agent that strongly reduces thyroid hormone levels. Synthesis of these hormones is catalyzed in vivo by thyroid peroxidase. The interaction of this drug with molecular iodine and its effect on peroxidase activity were investigated. Iodine and 2-thiazoline-2-thiol form a complex of the charge transfer type of 1:1 stoichiometry characterized by a formation constant of 2,527 l.mole-1 at 20 degrees C. This drug was found to inhibit both horseradish peroxidase and lactoperoxidase (used as a model of thyroid peroxidase) in a competitive manner, giving inhibition constants of 5.7 mM and 0.13 mM, respectively. T3 and T4 levels were reduced significantly after a three-week administration of this drug to a group of 10 rats. Histological examination of the thyroid gland showed the presence of a cylindrical epithelium, which is indicative of hyperactivity of the gland. The results indicated that 2-thiazoline-2-thiol acts on both molecular iodine and thyroid peroxidase.
Thomes
J C
JC
Department of Chemical Pharmacy, Faculty of Pharmacy, University of Limoges, France.
Comby
F
F
Lagorce
J F
JF
Buxeraud
J
J
Raby
C
C
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D007455:Iodine / Q000494:pharmacology; D008297:Male; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D013844:Thiazoles / Q000494:pharmacology*; D053778:Thiazolidines; D013963:Thyroid Hormones / Q000096:biosynthesis*; D013974:Thyroxine / Q000096:biosynthesis; D014284:Triiodothyronine / Q000096:biosynthesis
D013956:Antithyroid Agents; D013844:Thiazoles; D053778:Thiazolidines; D013963:Thyroid Hormones; D014284:Triiodothyronine; C005104:2-mercaptothiazoline; D007455:Iodine; D010544:Peroxidases; D013974:Thyroxine