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Int. J. Mol. Sci. 2015, 16(12), 28534-28548;

Repositioning of Thiourea-Containing Drugs as Tyrosinase Inhibitors

Research Institute of Pharmaceutical Sciences, College of Pharmacy, Kyungpook National University, 80 Daehak-ro, Buk-gu, Daegu 702-701, Korea
Author to whom correspondence should be addressed.
Academic Editor: Christo Z. Christov
Received: 15 November 2015 / Revised: 22 November 2015 / Accepted: 24 November 2015 / Published: 2 December 2015
PDF [4749 KB, uploaded 2 December 2015]


Tyrosinase catalyzes two distinct sequential reactions in melanin biosynthesis: The hydroxylation of tyrosine to dihydroxyphenylalanine (DOPA) and the oxidation of DOPA to dopaquinone. Developing functional modulators of tyrosinase is important for therapeutic and cosmetic purposes. Given the abundance of thiourea moiety in known tyrosinase inhibitors, we studied other thiourea-containing drugs as potential tyrosinase inhibitors. The thiourea-containing drugs in clinical use were retrieved and tested for their ability to inhibit tyrosinase. We observed that methimazole, thiouracil, methylthiouracil, propylthiouracil, ambazone, and thioacetazone inhibited mushroom tyrosinase. Except for methimazole, there was limited information regarding the activity of other drugs against tyrosinase. Both thioacetazone and ambazone significantly inhibited tyrosinase, with IC50 of 14 and 15 μM, respectively. Ambazone decreased melanin content without causing cellular toxicity at 20 μM in B16F10 cells. The activity of ambazone was stronger than that of kojic acid both in enzyme and melanin content assays. Kinetics of enzyme inhibition assigned the thiourea-containg drugs as non-competitive inhibitors. The complex models by docking simulation suggested that the intermolecular hydrogen bond via the nitrogen of thiourea and the contacts via thione were equally important for interacting with tyrosinase. These data were consistent with the results of enzyme assays with the analogues of thiourea. View Full-Text
Keywords: cheminformatics; docking simulation; drug repositioning; thiourea; tyrosinase cheminformatics; docking simulation; drug repositioning; thiourea; tyrosinase

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Choi, J.; Jee, J.-G. Repositioning of Thiourea-Containing Drugs as Tyrosinase Inhibitors. Int. J. Mol. Sci. 2015, 16, 28534-28548.

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