| Autor: |
Jeongin Ko, Jieun Lee, Hee Jin Jung, Sultan Ullah, Yeongmu Jeong, Sojeong Hong, Min Kyung Kang, Yu Jung Park, YeJi Hwang, Dongwan Kang, Yujin Park, Pusoon Chun, Jin-Wook Yoo, Hae Young Chung, Hyung Ryong Moon |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Antioxidants, Vol 11, Iss 10, p 1918 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2076-3921 |
| DOI: |
10.3390/antiox11101918 |
| Popis: |
Many compounds containing the β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold, including cinnamamide derivatives, have been shown to inhibit tyrosinase potently in vitro and in vivo. Structural changes to cinnamamide derivatives were produced by adding a dithionate functional group to provide eight (Z)-5-(substituted benzylidene)-3-cyclohexyl-2-thioxothiazolidin-4-one analogs with high log p values for skin. These analogs were synthesized using a two-step reaction, and their stereochemistry was confirmed using the 3JC4-Hβ values of C4 measured in proton-coupled 13C mode. Analogs 2 (IC50 = 5.21 ± 0.86 µM) and 3 (IC50 = 1.03 ± 0.14 µM) more potently inhibited mushroom tyrosinase than kojic acid (IC50 = 25.26 ± 1.10 µM). Docking results showed 2 binds strongly to the active site of tyrosinase, while 3 binds strongly to an allosteric site. Kinetic studies using l-tyrosine as substrate indicated 2 and 3 competitively and non-competitively inhibit tyrosinase, respectively, which was supported by our docking results. In B16F10 cells, 3 significantly and concentration-dependently reduced α–MSH plus IBMX induced increases in cellular tyrosinase activity and melanin production and the similarity between these inhibitory patterns implied that the anti-melanogenic effect of 3 might be due to its tyrosinase-inhibitory ability. In addition, 2 and 3 exhibited strong antioxidant effects; for example, they reduced ROS and ONOO– levels and exhibited radical scavenging activities, suggesting that these effects might underlie their anti-melanogenic effects. Furthermore, 3 suppressed the expressions of melanogenesis-associated proteins and genes in B16F10 cells. These results suggest (Z)-5-(substituted benzylidene)-3-cyclohexyl-2-thioxothiazolidin-4-one analogs offer a means of producing novel anti-melanogenesis agents. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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