What is 2-Thiouracil?

Fig 1. Chemical structure formula and three-dimensional structure of 2-Thiouracil

2-Thiouracil is a sulfur-containing uracil. An established antithyroid drug and highly selective inhibitor of nitric oxide synthase (NOS), 2-thiouracil also covalently binds to dopaquinone, produced by tyrosinase catalyzed oxidation of tyrosine, thereby selectively accumulating in de novo-synthesized melanin in overactive melanin-producing cells and providing a means to localize melanoma cells.2-Thiouracil is a nucleobase analogue that is uracil in which the oxo group at C-2 is replaced by a thioxo group. It has a role as an antithyroid drug and a metabolite. It is a thiocarbonyl compound and a nucleobase analogue. It derives from a uracil.

2-Thiouracil is a thiolated uracil derivative that is a known antihyperthyroid agent. 2-Thiouracil is an established antithyroid drug and an extensively investigated agent for the early detection and targeting of metastatic melanotic melanoma. In addition, 2-Thiouracil is also a selective inhibitor of neuronal nitric oxide synthase antagonising tetrahydrobiopterin-dependent enzyme activation and dimerization. 2-Thiouracil refers both to a specific molecule consisting of a sulfated uracil, and a family of molecules based upon that structure. 2-Thiouracil inhibits thyroid activity by blocking the enzyme thyroid peroxidase[1-3].

2-Thiouracil inhibits thyroid activity by blocking the enzyme thyroid peroxidase.[2] Its use in recent times has been replaced by advent of more potent and safer antithyroid drugs. It occurs in seeds of Brassica and Crucifera species. 2-Thiouracil has been used as antithyroid, coronary vasodilator, and in congestive heart failure although its use has been largely supplanted by other drugs.

2-Thiouracil is an established antithyroid pyrimidine analog and an extensively investigated agent for the early detection and targeting of metastatic melanotic melanoma. 2-thiouracil is effectively incorporated into the RNA and leads to alterations in the structure of the proteins synthesized. In addition, 2-Thiouracil is also a selective inhibitor of neuronal nitric oxide synthase antagonising tetrahydrobiopterin-dependent enzyme activation and dimerization[4].

2-thiouracil is a sulfated uracil typically used as an anti-thyroid agent for Graves’ disease by inhibiting the thyroid enzyme thyroid peroxidase. When given to lab animals it can induce arteriosclerosis.

2-Thiouracil has been used as antithyroid, coronary vasodilator, and in congestive heart failure although its use has been largely supplanted by other drugs. It is known to cause blood dyscrasias and suspected of terato- and carcinogenesis.

References

[1] Palumbo, A., M. d'Ischia, and F.A. Cioffi, 2-thiouracil is a selective inhibitor of neuronal nitric oxide synthase antagonising tetrahydrobiopterin-dependent enzyme activation and dimerisation. FEBS Lett, 2000. 485(2-3): p. 109-12.
[2] Napolitano, A., et al., Mechanism of selective incorporation of the melanoma seeker 2-thiouracil into growing melanin. J Med Chem, 1996. 39(26): p. 5192-201.
[3] Nagasaka, A. and H. Hidaka, Effect of antithyroid agents 6-propyl-2-thiouracil and 1-mehtyl-2-mercaptoimidazole on human thyroid iodine peroxidase. J Clin Endocrinol Metab, 1976. 43(1): p. 152-8.
[4] Beck C F , Howlett G J . The nature of the miscoding caused by growth in the presence of 2-thiouracil[J]. Journal of Molecular Biology, 1977, 111(1):1-17.
[5] https://pubchem.ncbi.nlm.nih.gov/compound/1269845
[6] https://www.chemspider.com/Chemical-Structure.1066108.html?rid=c759ed38-6265-41f5-ac99-5383245a0338