2-Thiouracil

2-Thiouracil is a thio-derivative of uracil, a pyrimidine nucleobase. It is an established antithyroid drug and melanoma seeker.

Thyroid peroxidase. In vitro, thiouracil irreversibly inactivated thyroid peroxidase when it was preincubated with the enzyme and hydrogen peroxide without iodide or another oxidisable substrate. Iodide or thiocyanate prevented this inactivation.

Neuronal nitric oxide synthase. In vitro, 2-thiouracil was found to inhibit neuronal nitric oxide synthase selectively and competitively, and it was inactive on the other NOS isoforms. It apparently interfered with substrate and tetrahydrobiopterin binding, and it antagonised tetrahydrobiopterin-induced dimerisation of the enzyme.

Melanin research. 2-Thiouracil is generally recognised as a highly specific melanoma seeker because it is selectively accumulated into active melanin-producing tissues. In vitro, it reacts with dopaquinone, an early intermediate in melanin biosynthesis, to give the addition product 6-S-thiouracildopa.

Its proposed route into growing melanin is nucleophilic attack of the thioureylene group on quinonoid intermediates of the melanin pathway, chiefly dopaquinone and 5,6-indolequinones.

Excited-state dynamics. The ultrafast internal conversion and intersystem crossing dynamics of 2-thiouracil have been studied by time-resolved photoelectron spectroscopy. Like other thiobases, it populates the triplet manifold with high quantum yields through the lowest singlet excited state.