Repositioning of thiourea-containing drugs as tyrosinase inhibitors

Joonhyeok Choi, Jun Goo Jee

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)28534-28548
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume16
Issue number12
DOIs
StatePublished - 2 Dec 2015

Keywords

  • Cheminformatics
  • Docking simulation
  • Drug repositioning
  • Thiourea
  • Tyrosinase

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