Synthesis and anti-tyrosinase mechanism of the substituted vanillyl cinnamate analogues

Zhao, Zhengyan; Liu, Guangxin; Meng, Yufeng; Tian, Jiale; Chen, Xufei; Shen, Meilun; Li, Yuexuan; Li, Bingyao; Gao, Cong; Wu, Shaoping; Li, Cuiqin; He, Xirui; Jiang, Ru; Qian, Mingcheng; Zheng, Xiaohui

doi:10.1016/j.bioorg.2019.103316

Cited by 22 publications

(7 citation statements)

References 38 publications

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“…The mechanical structures of the small molecules were optimized using ChemBio3D Ultra 14.0. The 3D crystal structure of mushroom TYR (PDB ID: 2Y9X, docking coordinates: X = −8.87, Y = −30.74, and Z = −41.52) was obtained from the Protein Data Bank (PDB) database [ 36 ]. The 3D crystal structures of six membrane receptors (opioid u receptor, PDB ID: 4DKI; melanocortin 1 receptor, PDB ID: 2L1J; endothelin B receptor, PDB ID: 5GLI; adrenergic β receptor, PDB ID: 4GBR; prostaglandin receptor, PDB ID: 6D26; stem cell factor receptor, PDB ID: 2EC8) were obtained from the PDB database.…”

Section: Methodsmentioning

confidence: 99%

Identification of Sitogluside as a Potential Skin‐Pigmentation‐Reducing Agent through Network Pharmacology

Guo

Zeng

et al. 2021

Oxidative Medicine and Cellular Longevity

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Many traditional Chinese medicines (TCMs) with skin-whitening properties have been recorded in the Ben-Cao-Gang-Mu and in folk prescriptions, and some literature confirms that their extracts do have the potential to inhibit pigmentation. However, no systematic studies have identified the specific regulatory mechanisms of the potential active ingredients. The aim of this study was to screen the ingredients in TCMs that inhibit skin pigmentation through a network pharmacology system and to explore underlying mechanisms. We identified 148 potential active ingredients from 14 TCMs, and based on the average “degree” of the topological parameters, the top five TCMs (Fructus Ligustri Lucidi, Hedysarum multijugum Maxim., Ampelopsis japonica, Pseudobulbus Cremastrae Seu Pleiones, and Paeoniae Radix Alba) that were most likely to cause skin-whitening through anti-inflammatory processes were selected. Sitogluside, the most common ingredient in the top five TCMs, inhibits melanogenesis in human melanoma cells (MNT1) and murine melanoma cells (B16F0) and decreases skin pigmentation in zebrafish. Furthermore, mechanistic research revealed that sitogluside is capable of downregulating tyrosinase (TYR) expression by inhibiting the ERK and p38 pathways and inhibiting TYR activity. These results demonstrate that network pharmacology is an effective tool for the discovery of natural compounds with skin-whitening properties and determination of their possible mechanisms. Sitogluside is a novel skin-whitening active ingredient with dual regulatory effects that inhibit TYR expression and activity.

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Section: Methodsmentioning

confidence: 99%

Identification of Sitogluside as a Potential Skin‐Pigmentation‐Reducing Agent through Network Pharmacology

Guo

Zeng

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…For the docking interaction energy score, the targets were ranked as PTGS2 > SRC > ESR1 > EGFR (Table 1). The carbonyl, methoxy and hydroxy groups are thought to be the key groups that bind residues containing H donor moieties at the terminus (Zhao et al, 2019); (Lin et al, 2019); (Duan et al, 2014); (De Savi et al, 2015); (Blobaum et al, 2015) For the specific proteins in the EGFR complex, the residues involved in the formation of H-bonds included ALA 743, THR 790, VAL726, and THR 854. With regard to the SRC docking results, the key residues involved in H-bonds were MET 341, VAL 281 and LEU 393.…”

Section: Molecular Docking and Experimental Validation Of The Binding Of Core Acacetin Targets Predicted By Network Pharmacologymentioning

confidence: 99%

A Systematic Study of the Mechanism of Acacetin Against Sepsis Based on Network Pharmacology and Experimental Validation

et al. 2021

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Sepsis is a dysregulated systemic response to infection, and no effective treatment options are available. Acacetin is a natural flavonoid found in various plants, including Sparganii rhizoma, Sargentodoxa cuneata and Patrinia scabiosifolia. Studies have revealed that acacetin potentially exerts anti-inflammatory and antioxidative effects on sepsis. In this study, we investigated the potential protective effect of acacetin on sepsis and revealed the underlying mechanisms using a network pharmacology approach coupled with experimental validation and molecular docking. First, we found that acacetin significantly suppressed pathological damage and pro-inflammatory cytokine expression in mice with LPS-induced fulminant hepatic failure and acute lung injury, and in vitro experiments further confirmed that acacetin attenuated LPS-induced M1 polarization. Then, network pharmacology screening revealed EGFR, PTGS2, SRC and ESR1 as the top four overlapping targets in a PPI network, and GO and KEGG analyses revealed the top 20 enriched biological processes and signalling pathways associated with the therapeutic effects of acacetin on sepsis. Further network pharmacological analysis indicated that gap junctions may be highly involved in the protective effects of acacetin on sepsis. Finally, molecular docking verified that acacetin bound to the active sites of the four targets predicted by network pharmacology, and in vitro experiments further confirmed that acacetin significantly inhibited the upregulation of p-src induced by LPS and attenuated LPS-induced M1 polarization through gap junctions. Taken together, our results indicate that acacetin may protect against sepsis via a mechanism involving multiple targets and pathways and that gap junctions may be highly involved in this process.

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“…To further study the binding mode of the bitopic ligands with D 2 R, we performed molecular docking experiments via Discovery Studio 2020 (DS2020) as described previously. [9,10] The crystal structure of D 2 R (PDB code: 6CM4) was downloaded from protein databank (PDB website). Then, the selected compounds 5 b and 11 b and their lead compound 2 were docked to D 2 R (Figure 2).…”

Section: Molecular Modeling Studymentioning

confidence: 99%

“…Finally, the prepared protein and ligands were used for the docking study via LibDock and CDOCKER of DS2020 as described previously. [9,10]…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Synthesis of Bitopic Ligands as Potent Dopamine D₂ Receptor Agonists

Qian

Zhou

et al. 2021

ChemMedChem

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In this study, we designed and synthesized twelve bitopic ligands as dopamine D 2 receptor (D 2 R) agonists. The forskolin-induced cAMP accumulation assay revealed that all the finial compounds are able to activate D 2 R. Furthermore, bitopic ligand N-((trans)-4-showed 21-fold higher potency than lead compound propyl aminoindane (2) and 17-fold higher subtype selectivity for D 2 R over D 4 R, indicating that the optimal length of spacer affects the D 2 R functionality. Molecular modeling study exhibited that 11 b formed an electrostatic interaction and two H-bonds with amino acid Asp114, which contributes significantly to the D 2 R functional activity. Taken together, we discovered a bitopic ligand 11 b as potent D 2 R agonist, which may be used as a tool compound for further study.

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Synthesis and anti-tyrosinase mechanism of the substituted vanillyl cinnamate analogues

Cited by 22 publications

References 38 publications

Identification of Sitogluside as a Potential Skin‐Pigmentation‐Reducing Agent through Network Pharmacology

Identification of Sitogluside as a Potential Skin‐Pigmentation‐Reducing Agent through Network Pharmacology

A Systematic Study of the Mechanism of Acacetin Against Sepsis Based on Network Pharmacology and Experimental Validation

Synthesis of Bitopic Ligands as Potent Dopamine D₂ Receptor Agonists

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Synthesis and anti-tyrosinase mechanism of the substituted vanillyl cinnamate analogues

Cited by 22 publications

References 38 publications

Identification of Sitogluside as a Potential Skin‐Pigmentation‐Reducing Agent through Network Pharmacology

Identification of Sitogluside as a Potential Skin‐Pigmentation‐Reducing Agent through Network Pharmacology

A Systematic Study of the Mechanism of Acacetin Against Sepsis Based on Network Pharmacology and Experimental Validation

Synthesis of Bitopic Ligands as Potent Dopamine D2 Receptor Agonists

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Synthesis of Bitopic Ligands as Potent Dopamine D₂ Receptor Agonists