Synthesis and Biological Activity Evaluation of 2-Cyanopyrrole Derivatives as Potential Tyrosinase Inhibitors

Hu, Yuwen; Gao, Zhu-Peng; Zheng, Yingying; Hu, Chunmei; Lin, Jing; Wu, Xiao-Zheng; Zhang, Xin; Zhou, Yongsheng; Xiong, Zhuang; Zhu, Dongsheng

doi:10.3389/fchem.2022.914944

Cited by 7 publications

(6 citation statements)

References 35 publications

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“…Compounds c1 ~ c29 were tested for their tyrosinase inhibitory activities according to previous reports [ 53 , 54 ]. Each compound was dissolved in DMSO and diluted to different concentrations.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…The para hydroxy phenyl substitution significantly improved the activity (Figure 6). Zhu et al synthesized a series of 2-cyanopyrrole derivatives (13-14, Figure 5) as TYRIs [24]. IC 50 values from 0.97 to >200 µM were shown on diphenolase activity, compared to kojic acid (5, IC 50 = 28.72 µM).…”

Section: Indole Derivativesmentioning

confidence: 99%

Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances

Vittorio

Dank

Ielo

2023

IJMS

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Tyrosinase is a copper-containing enzyme which is widely distributed in nature (e.g., bacteria, mammals, fungi) and involved in two consecutive steps of melanin biosynthesis. In humans, an excessive production of melanin can determine hyperpigmentation disorders as well as neurodegenerative processes in Parkinson’s disease. The development of molecules able to inhibit the high activity of the enzyme remain a current topic in medicinal chemistry, because the inhibitors reported so far present several side effects. Heterocycle-bearing molecules are largely diffuse in this sense. Due to their importance as biologically active compounds, we decided to report a comprehensive review of synthetic tyrosinase inhibitors possessing heterocyclic moieties reported within the last five years. For the reader’s convenience, we classified them as inhibitors of mushroom tyrosinase (Agaricus bisporus) and human tyrosinase.

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“…Imidazole derivatives are important among heterocycles found as active tyrosinase inhibitors. [15,16] On the other hand, metronidazole (MTZ), an important bactericidal compound, was found useful against various…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Metronidazole and Heterocycle Ester Dyads for Tyrosinase Inhibitory Activity

Elavarasu,

Senthil

2024

Int. J. Pharm. Sci. Drug Res.

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Tyrosinase is an important copper-based enzyme mainly involved in skin pigmentation. The inhibition of the tyrosinase enzyme attracts importance in cosmetic and medicinal chemistry industry for its applications in skin whitening and anti-browning agents for humans as well as in food, agriculture industries. Imidazole based Metronidazole and its derivatives are widely accepted drug for wide range of diseases. Therefore, the present report involves the synthesis of heterocyclic derivatives of metronidazole and investigation of its efficacy towards the tyrosinase inhibitory activity. A series of metronidazole esters were synthesized and their chemical structures were confirmed using spectral techniques like, infrared spectroscopy (IR), proton nuclear magnetic resonance (1H-NMR), and liquid chromatography-mass spectrometry (LC-MS). All the compounds were evaluated for its tyrosinase inhibitory activity by oxidation of 3,4-dihydroxyphenylalanine in the presence of the synthesized esters(I-VIII) with kojic acid as standard. Among the synthesized compounds, VII (isonicotinic ester) and VIII (quinoline ester) demonstrated significant activity IC50 values 92.5 and 91.8µM respectively. Further molecular docking experiments were carried out for the synthesized compounds with 2y9w protein exhibited greater number of physical interactions for compounds VII and VIII than the other compounds in the series confirming the mushroom tyrosinase activity.

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Synthesis and Biological Activity Evaluation of 2-Cyanopyrrole Derivatives as Potential Tyrosinase Inhibitors

Cited by 7 publications

References 35 publications

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

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

Heterocyclic Compounds as Synthetic Tyrosinase Inhibitors: Recent Advances

Synthesis and Characterization of Metronidazole and Heterocycle Ester Dyads for Tyrosinase Inhibitory Activity

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