Design and synthesis of thiourea derivatives with sulfur-containing heterocyclic scaffolds as potential tyrosinase inhibitors |
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Institution: | 1. Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Gründenstrasse 40, CH-4132 Muttenz, Switzerland;2. Institute of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland;3. AgroBioInstitute, Agriculture Academy, Dragan Tzankov 8, Sofia 1164, Bulgaria |
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Abstract: | Tyrosinase is a key enzyme during the production of melanins in plants and animals. A class of novel N-aryl-N′-substituted phenylthiourea derivatives (3a–i, 6a–k) were designed, synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were evaluated. The results showed some 4,5,6,7-tetrahydro-2-(phenylamino)thioxomethyl]amino]-benzob]thiophene-3-carboxylic acid derivatives (3a–i) exhibited moderate inhibitory potency on diphenolase activity of tyrosinase. When the scaffold of 4,5,6,7-tetrahydrobenzob]thiophene-3-carboxylic acid was replaced with 2-(1,3,4-thiadiazol-2-yl)thio acetic acid, the inhibitory activity of compounds (6a–k) against tyrosinase was improved obviously; especially, the inhibitory activity of compound 6h (IC50 = 6.13 μM) is significantly higher than kojic acid (IC50 = 33.3 μM). Moreover, the analysis on inhibition mechanism revealed that compound 6h might plays the role as a noncompetitive inhibitor. |
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Keywords: | Tyrosinase Inhibition Thiourea derivatives Thiadiazol Thiophene |
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