Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation

Xue, Songtao; Li, Zhiwei; Ze, Xiaotong; Xiuyuan, Wu; He, Chen; Wen, Shuai; Marlow, Maria; Chen, Jian; Scurr, David J.; Zhu, Zheying; Xu, Jinyi; Xu, Shengtao

doi:10.1021/acs.jmedchem.3c00012

Cited by 12 publications

(6 citation statements)

References 64 publications

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“…To the 3.0 mL of tyrosinase solution, 1 μL of quercetagetin was added. 3D fluorescence spectra were measured (Wu X. et al, 2023).…”

Section: D Fluorescence Spectramentioning

confidence: 99%

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

Liang

2024

Front. Chem.

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Tyrosinase is one important rate limiting enzyme in melanin synthesis, directly affecting the melanin synthesis. Quercetagetin is one active ingredient from marigold. Thence, the inhibition effects of quercetagetin against tyrosinase were investigated. The results showed quercetagetin could inhibit tyrosinase activity with IC50 value of 0.19 ± 0.01 mM and the inhibition type was a reversible mixed-type. Results of fluorescence quenching showed quercetagetin could quench tyrosinase fluorescence in static process. CD and 3D fluorescence results showed the interaction of quercetagetin to tyrosinase could change tyrosinase conformation to inhibit activity. Moreover, docking revealed details of quercetagetin’s interactions with tyrosinase.

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“…To the 3.0 mL of tyrosinase solution, 1 μL of quercetagetin was added. 3D fluorescence spectra were measured (Wu X. et al, 2023).…”

Section: D Fluorescence Spectramentioning

confidence: 99%

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

Liang

2024

Front. Chem.

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“…The browning of fruits and fungi after the harvest of crops such as mushrooms and that of beverages are also due to an abnormal level of tyrosine in plants [ 6 ]. Women are vulnerable to dermatological disorders such as freckles, senile lentigo, pigmented acne scars, and melasma, and these hyper-pigmentation conditions are directly associated with hyper-accumulation of melanin [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Synergistic Biomedical Potential and Molecular Docking Analyses of Coumarin–Triazole Hybrids as Tyrosinase Inhibitors: Design, Synthesis, In Vitro Profiling, and In Silico Studies

Kausar,

Zahoor,

Tabassum

et al. 2024

Pharmaceuticals

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The tyrosinase enzyme has a vital role in the browning of vegetables and fruits and the biosynthesis of melanin. In this work, we synthesized a diverse library of coumarin–triazole hybrids, and these compounds were characterized by using suitable analytical techniques. Our research work extends beyond the synthetic effort to explore the therapeutic potential of these compounds. We put the synthesized compounds through meticulous in vitro screening against the tyrosinase enzyme, and these coumarin derivatives evinced good IC50 values in the range of 0.339 ± 0.25 µM to 14.06 ± 0.92 µM. In the library of synthesized compounds, six compounds were found to be more potent than standard ascorbic acid (IC50 = 11.5 ± 1.00), and among them, 17e and 17f, being the most active, exhibited remarkable anti-tyrosinase potential, with IC50 values of 0.339 ± 0.25 μM and 3.148 ± 0.23 μM, respectively. Furthermore, an in silico modeling study was carried out to determine the key interactions of these compounds with the tyrosinase protein (PDB ID: 2Y9X) and thus to authenticate our experimental findings. The quantitative SAR studies exhibited a good correlation between the synthesized derivatives of coumarin and their anti-tyrosinase activity. The docking studies verified the experimental results, and ligand 17e showed good interaction with the core residues of tyrosinase. This study not only expands the field of coumarin–triazole hybrid synthesis but also provides valuable insights for the development of novel tyrosinase inhibitors.

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“…Tyrosinase (EC 1.14.18.1), which is one kind of copper-containing metalloenzyme, widely exists in nature animals and plants [ 1 , 2 , 3 ]. Tyrosinase plays crucial roles in mediating the production of melanin pigment via two steps [ 4 , 5 , 6 , 7 , 8 ]. In the melanin process, tyrosinase monophenolase firstly catalyzes the hydroxylation of L-tyrosine to yield L-DOPA, which is further oxidized into o -dopaquinone by tyrosinase diphenolase ( Figure 1 ) [ 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

Min

Zheng

et al. 2023

Molecules

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Tyrosinase plays crucial roles in mediating the production of melanin pigment; thus, its inhibitors could be useful in preventing melanin-related diseases. To find potential tyrosinase inhibitors, a series of cinnamic acid–eugenol esters (c1~c29) was synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR, HRMS, and FT-IR, respectively. The biological evaluation results showed that all compounds c1~c29 exhibited definite tyrosinase inhibitory activity; especially, compound c27 was the strongest tyrosinase inhibitor (IC50: 3.07 ± 0.26 μM), being ~4.6-fold stronger than the positive control, kojic acid (IC50: 14.15 ± 0.46 μM). Inhibition kinetic studies validated compound c27 as a reversible mixed-type inhibitor against tyrosinase. Three-dimensional fluorescence and circular dichroism (CD) spectra results indicated that compound c27 could change the conformation and secondary structure of tyrosinase. Fluorescence-quenching results showed that compound c27 quenched tyrosinase fluorescence in the static manner with one binding site. Molecular docking results also revealed the binding interactions between compound c27 and tyrosinase. Therefore, cinnamic acid–eugenol esters, especially c27, could be used as lead compounds to find potential tyrosinase inhibitors.

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Design, Synthesis, and Biological Evaluation of Novel Hybrids Containing Dihydrochalcone as Tyrosinase Inhibitors to Treat Skin Hyperpigmentation

Cited by 12 publications

References 64 publications

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

Synergistic Biomedical Potential and Molecular Docking Analyses of Coumarin–Triazole Hybrids as Tyrosinase Inhibitors: Design, Synthesis, In Vitro Profiling, and In Silico Studies

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

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