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Inhibition of Human Tyrosinase Requires Molecular Motifs Distinctively Different from Mushroom Tyrosinase
- Source :
- Journal of Investigative Dermatology. 138:1601-1608
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Tyrosinase is the rate-limiting enzyme of melanin production and, accordingly, is the most prominent target for inhibiting hyperpigmentation. Numerous tyrosinase inhibitors have been identified, but most of those lack clinical efficacy because they were identified using mushroom tyrosinase as the target. Therefore, we used recombinant human tyrosinase to screen a library of 50,000 compounds and compared the active screening hits with well-known whitening ingredients. Hydroquinone and its derivative arbutin only weakly inhibited human tyrosinase with a half-maximal inhibitory concentration (IC50) in the millimolar range, and kojic acid showed a weak efficacy (IC50 > 500 μmol/L). The most potent inhibitors of human tyrosinase identified in this screen were resorcinyl-thiazole derivatives, especially the newly identified Thiamidol (Beiersdorf AG, Hamburg, Germany) (isobutylamido thiazolyl resorcinol), which had an IC50 of 1.1 μmol/L. In contrast, Thiamidol only weakly inhibited mushroom tyrosinase (IC50 = 108 μmol/L). In melanocyte cultures, Thiamidol strongly but reversibly inhibited melanin production (IC50 = 0.9 μmol/L), whereas hydroquinone irreversibly inhibited melanogenesis (IC50 = 16.3 μmol/L). Clinically, Thiamidol visibly reduced the appearance of age spots within 4 weeks, and after 12 weeks some age spots were indistinguishable from the normal adjacent skin. The full potential of Thiamidol to reduce hyperpigmentation of human skin needs to be explored in future studies.
- Subjects :
- Male
0301 basic medicine
Tyrosinase
Skin Lightening Preparations
Drug Evaluation, Preclinical
Dermatology
Melanocyte
Biochemistry
Substrate Specificity
Fungal Proteins
Tissue Culture Techniques
Melanin
Inhibitory Concentration 50
03 medical and health sciences
chemistry.chemical_compound
Species Specificity
Hyperpigmentation
medicine
Animals
Humans
Enzyme Inhibitors
Molecular Biology
IC50
Aged
Skin
Melanins
chemistry.chemical_classification
Molecular Structure
Monophenol Monooxygenase
Arbutin
Cell Biology
Middle Aged
Recombinant Proteins
High-Throughput Screening Assays
Skin Aging
Molecular Docking Simulation
HEK293 Cells
Treatment Outcome
030104 developmental biology
medicine.anatomical_structure
Enzyme
chemistry
Female
medicine.symptom
Agaricales
Kojic acid
Subjects
Details
- ISSN :
- 0022202X
- Volume :
- 138
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....5cd7c2f1e68f42c68e8dc31ad61c3978