Repositioning of Thiourea-Containing Drugs as Tyrosinase Inhibitors
| العنوان: | Repositioning of Thiourea-Containing Drugs as Tyrosinase Inhibitors |
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| المؤلفون: | Joonhyeok Choi, Jun-Goo Jee |
| المصدر: | International Journal of Molecular Sciences Volume 16 Issue 12 Pages 28534-28548 International Journal of Molecular Sciences, Vol 16, Iss 12, Pp 28534-28548 (2015) International Journal of Molecular Sciences; Volume 16; Issue 12; Pages: 28534-28548 |
| بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Models, Molecular, Ambazone, Mitoguazone, Cell Survival, cheminformatics, docking simulation, drug repositioning, thiourea, tyrosinase, Tyrosinase, Melanoma, Experimental, Molecular Conformation, Catalysis, Article, Inorganic Chemistry, Hydroxylation, Melanin, lcsh:Chemistry, chemistry.chemical_compound, Mice, Cell Line, Tumor, Animals, Humans, Physical and Theoretical Chemistry, Enzyme Inhibitors, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, Melanins, Dose-Response Relationship, Drug, Monophenol Monooxygenase, Organic Chemistry, General Medicine, Thiouracil, Computer Science Applications, Kinetics, Enzyme, chemistry, Biochemistry, Thiourea, lcsh:Biology (General), lcsh:QD1-999, Kojic acid, Protein Binding |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| DOI: | 10.3390/ijms161226114 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::abbbee02714e83193cf71d70605ca6deTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....abbbee02714e83193cf71d70605ca6de |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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| DOI: | 10.3390/ijms161226114 |