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| Main Authors: | , , , , , , , , , |
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| Format: | Artículo científico |
| Language: | en |
| Published: |
International journal of biological macromolecules
2025
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| Subjects: | |
| Online Access: | https://pubmed.ncbi.nlm.nih.gov/40020832/ |
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| _version_ | 1868266237314727936 |
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| author | Yang, Chunyan Lai, Huixian Yang, Xiaoyu Huang, Yuehong Shi, Yan Ke, Lina Chen, Lizhu Chen, Mingliang Chen, Hongbin Wang, Qin |
| author_facet | Yang, Chunyan Lai, Huixian Yang, Xiaoyu Huang, Yuehong Shi, Yan Ke, Lina Chen, Lizhu Chen, Mingliang Chen, Hongbin Wang, Qin Yang, Chunyan Lai, Huixian Yang, Xiaoyu Huang, Yuehong Shi, Yan Ke, Lina Chen, Lizhu Chen, Mingliang Chen, Hongbin Wang, Qin |
| collection | PubMed - marine biology |
| contents | Unveiling an indole derivative YM818 as a novel tyrosinase inhibitor with anti-melanogenic and anti-melanin transfer effects. Yang, Chunyan Lai, Huixian Yang, Xiaoyu Huang, Yuehong Shi, Yan Ke, Lina Chen, Lizhu Chen, Mingliang Chen, Hongbin Wang, Qin Monophenol Monooxygenase Melanins Animals Zebrafish Indoles Enzyme Inhibitors Humans Molecular Docking Simulation Mice Indole and its derivatives, heterocyclic compounds with broad therapeutic potential, have seen limited study in melanogenesis. Here, our virtual screening identified 15 indole derivatives that potentially interacted with tyrosinase (TYR), a key enzyme in melanogenesis. Nine of the 15 indole derivatives tested significantly decreased tyrosinase activity, and 3-hydroxy-5-bromo-(3-indolyl)-2‑carbonyl indole (designated as YM818) exhibited highest inhibitory rate at 74.28 % with IC of 0.372 mmol/L. Surface plasmon resonance and fluorescence quenching assays demonstrated the direct interaction between YM818 and TYR with K value 94.84 ± 45.27 μmol/L. YM818 treatment reduced cellular melanin content to 35.8 %. Furthermore, YM818 treatment enhanced AKT protein phosphorylation, leading to the downregulation of melanogenesis-related proteins, including MITF, TYR and TRP1. In vivo zebrafish studies confirmed the inhibitory effects of YM818 on melanogenesis. Additionally, YM818 disrupted melanin transfer by suppressing the expression of protease-activated receptor-2 (PAR-2) gene, a G protein-coupled receptor that plays a crucial role in mediating cellular responses to serine proteases, including keratinocyte phagocytosis and melanin transfer. YM818 also exhibited robust antioxidant activity, with 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging IC values comparable to vitamin C and significantly reducing intracellular ROS levels in a dose-dependent manner. Taken together, these findings highlight YM818 as a promising anti-melanogenic agent, offering valuable insights into the development of novel anti-melanin drugs and tyrosinase inhibitors. |
| format | Artículo científico |
| id | pubmed_40020832 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | International journal of biological macromolecules |
| record_format | pubmed |
| spellingShingle | Unveiling an indole derivative YM818 as a novel tyrosinase inhibitor with anti-melanogenic and anti-melanin transfer effects. Yang, Chunyan Lai, Huixian Yang, Xiaoyu Huang, Yuehong Shi, Yan Ke, Lina Chen, Lizhu Chen, Mingliang Chen, Hongbin Wang, Qin Monophenol Monooxygenase Melanins Animals Zebrafish Indoles Enzyme Inhibitors Humans Molecular Docking Simulation Mice Unveiling an indole derivative YM818 as a novel tyrosinase inhibitor with anti-melanogenic and anti-melanin transfer effects. Yang, Chunyan Lai, Huixian Yang, Xiaoyu Huang, Yuehong Shi, Yan Ke, Lina Chen, Lizhu Chen, Mingliang Chen, Hongbin Wang, Qin Monophenol Monooxygenase Melanins Animals Zebrafish Indoles Enzyme Inhibitors Humans Molecular Docking Simulation Mice Indole and its derivatives, heterocyclic compounds with broad therapeutic potential, have seen limited study in melanogenesis. Here, our virtual screening identified 15 indole derivatives that potentially interacted with tyrosinase (TYR), a key enzyme in melanogenesis. Nine of the 15 indole derivatives tested significantly decreased tyrosinase activity, and 3-hydroxy-5-bromo-(3-indolyl)-2‑carbonyl indole (designated as YM818) exhibited highest inhibitory rate at 74.28 % with IC of 0.372 mmol/L. Surface plasmon resonance and fluorescence quenching assays demonstrated the direct interaction between YM818 and TYR with K value 94.84 ± 45.27 μmol/L. YM818 treatment reduced cellular melanin content to 35.8 %. Furthermore, YM818 treatment enhanced AKT protein phosphorylation, leading to the downregulation of melanogenesis-related proteins, including MITF, TYR and TRP1. In vivo zebrafish studies confirmed the inhibitory effects of YM818 on melanogenesis. Additionally, YM818 disrupted melanin transfer by suppressing the expression of protease-activated receptor-2 (PAR-2) gene, a G protein-coupled receptor that plays a crucial role in mediating cellular responses to serine proteases, including keratinocyte phagocytosis and melanin transfer. YM818 also exhibited robust antioxidant activity, with 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging IC values comparable to vitamin C and significantly reducing intracellular ROS levels in a dose-dependent manner. Taken together, these findings highlight YM818 as a promising anti-melanogenic agent, offering valuable insights into the development of novel anti-melanin drugs and tyrosinase inhibitors. |
| title | Unveiling an indole derivative YM818 as a novel tyrosinase inhibitor with anti-melanogenic and anti-melanin transfer effects. |
| topic | Monophenol Monooxygenase Melanins Animals Zebrafish Indoles Enzyme Inhibitors Humans Molecular Docking Simulation Mice |
| url | https://pubmed.ncbi.nlm.nih.gov/40020832/ |