A Novel Class of Potent Anti-Tyrosinase Compounds with Antioxidant Activity, 2-(Substituted phenyl)-5-(trifluoromethyl)benzo[<i>d</i>]thiazoles: In Vitro and In Silico Insights
Sixteen compounds bearing a benzothiazole moiety were synthesized as potential tyrosinase inhibitors and evaluated for mushroom tyrosinase inhibitory activity. The compound 4-(5-(trifluoromethyl)benzo[<i>d</i>]thiazol-2-yl)benzene-1,3-diol (compound <b>1b</b>) exhibited the h...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Book |
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MDPI AG,
2022-07-01T00:00:00Z.
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| Summary: | Sixteen compounds bearing a benzothiazole moiety were synthesized as potential tyrosinase inhibitors and evaluated for mushroom tyrosinase inhibitory activity. The compound 4-(5-(trifluoromethyl)benzo[<i>d</i>]thiazol-2-yl)benzene-1,3-diol (compound <b>1b</b>) exhibited the highest tyrosinase activity inhibition, with an IC<sub>50</sub> value of 0.2 ± 0.01 μM (a potency 55-fold greater than kojic acid). In silico results using mushroom tyrosinase and human tyrosinase showed that the 2,4-hydroxyl substituents on the phenyl ring of <b>1b</b> played an important role in the inhibition of both tyrosinases. Kinetic studies on mushroom tyrosinase indicated that <b>1b</b> is a competitive inhibitor of monophenolase and diphenolase, and this was supported by docking results. In B16F10 murine melanoma cells, <b>1a</b> and <b>1b</b> dose-dependently and significantly inhibited melanin production intracellularly, and melanin release into medium more strongly than kojic acid, and these effects were attributed to the inhibition of cellular tyrosinase. Furthermore, the inhibition of melanin production by <b>1b</b> was found to be partially due to the inhibition of tyrosinase glycosylation and the suppression of melanogenesis-associated genes. Compound <b>1c</b>, which has a catechol group, exhibited potent antioxidant activities against ROS, DPPH, and ABTS, and <b>1b</b> also had strong ROS and ABTS radical scavenging activities. These results suggest that 5-(trifluoromethyl)benzothiazole derivatives are promising anti-tyrosinase lead compounds with potent antioxidant effects. |
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| Item Description: | 10.3390/antiox11071375 2076-3921 |