Design, synthesis and evaluation of cinnamic acid ester derivatives as mushroom tyrosinase inhibitors

Sheng, Zhaojun; Ge, Shanhai; Xu, Ximing; Zhang, Yan; Wu, Panpan; Zhang, Kun; Xu, Xuetao; Li, Chen; Zhao, Deng-Gao; Tang, Xiaowen

doi:10.1039/c8md00099a

Cited by 38 publications

(27 citation statements)

References 34 publications

(39 reference statements)

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“…In the last years several studies have been directed to the development of novel tyrosinase inhibitors inspired by natural scaffolds, which should overcome stability, efficacy, and isolation yield issues. One of the main exploited scaffolds is hydroxycinnamic acid: indeed several hydroxycinnamic acid analogues have been synthesized through the most disparate approaches [123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141], leading in some cases to very potent mushroom tyrosinase inhibitors (Figure 17), such as 2,4-dihydroxycinnamides (IC 50 = 0.0112-0.16 µM) [132,133]. A thiophenyl derivative of 2,4-dihydroxycinnamic acid has also exhibited a very low IC 50 value (0.013 µM) against the monophenolase activity of the enzyme [134].…”

Section: Synthetic Phenolic Inhibitors Of Mushroom Tyrosinasementioning

confidence: 99%

“…An IC50 value of 1.10 µM for the monophenolase activity of mushroom tyrosinase has been instead calculated for a cyclopentanone compound related to 3-hydroxy-4-methoxycinnamic acid [135]. Quite low IC 50 values have been reported also for dihydrolipoic acid conjugates of caffeic acid and its methylester [136,137], as well as for thiochromanone compounds [138], diamides [139], or esters [140,141]…”

Section: Synthetic Phenolic Inhibitors Of Mushroom Tyrosinasementioning

confidence: 99%

“…An IC50 value of 1.10 μM for the monophenolase activity of mushroom tyrosinase has been instead calculated for a cyclopentanone compound related to 3-hydroxy-4-methoxycinnamic acid [135]. Quite low IC50 values have been reported also for dihydrolipoic acid conjugates of caffeic acid and its methylester [136,137], as well as for thiochromanone compounds [138], diamides [139], or esters [140,141] related to p-coumaric acid. Similar scaffolds are chalcones [142][143][144][145][146][147][148][149][150][151][152][153][154][155][156], characterized by an enone moiety linked to a phenyl ring as well.…”

Section: Synthetic Phenolic Inhibitors Of Mushroom Tyrosinasementioning

confidence: 99%

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Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

2019

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One of the most common approaches for control of skin pigmentation involves the inhibition of tyrosinase, a copper-containing enzyme which catalyzes the key steps of melanogenesis. This review focuses on the tyrosinase inhibition properties of a series of natural and synthetic, bioinspired phenolic compounds that have appeared in the literature in the last five years. Both mushroom and human tyrosinase inhibitors have been considered. Among the first class, flavonoids, in particular chalcones, occupy a prominent role as natural inhibitors, followed by hydroxystilbenes (mainly resveratrol derivatives). A series of more complex phenolic compounds from a variety of sources, first of all belonging to the Moraceae family, have also been described as potent tyrosinase inhibitors. As to the synthetic compounds, hydroxycinnamic acids and chalcones again appear as the most exploited scaffolds. Several inhibition mechanisms have been reported for the described inhibitors, pointing to copper chelating and/or hydrophobic moieties as key structural requirements to achieve good inhibition properties. Emerging trends in the search for novel skin depigmenting agents, including the development of assays that could distinguish between inhibitors and potentially toxic substrates of the enzyme as well as of formulations aimed at improving the bioavailability and hence the effectiveness of well-known inhibitors, have also been addressed.

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Section: Synthetic Phenolic Inhibitors Of Mushroom Tyrosinasementioning

confidence: 99%

Section: Synthetic Phenolic Inhibitors Of Mushroom Tyrosinasementioning

confidence: 99%

Section: Synthetic Phenolic Inhibitors Of Mushroom Tyrosinasementioning

confidence: 99%

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Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

2019

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“…In other words, they inhibit the function of a-glucosidase by not only directly binding to free enzyme (EI), but also by interfering with the formation of the a-glucosidase-PNPG (ES) intermediate through producing an a-glucosidase-PNPG-inhibitor (ESI) complex in a noncompetitive manner 33 . The inhibition constant for the inhibitor binding with free enzyme (K i ) was determined from a plot of the slope (K m /V m ) versus the inhibitor concentration ( Figure 6(A2-D2)), and the inhibition constant for the inhibitor binding with enzyme-substrate complex (K is ) was obtained from the vertical intercept (1/V m ) versus the inhibitor concentration ( Figure 6(A3-D3)) 34 . The results are collected in Table 3: the K is values of all of them are smaller than their K i values, which mean that they have higher affinity with the enzyme-substrate complex than with the free enzyme.…”

Section: Inhibition Mechanismmentioning

confidence: 99%

Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives

Chen

Gao

Jian

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC 50 ¼ 4.2 lM) against a-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in a-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective a-glucosidase inhibitors, with IC 50 values at the micromolar level, especially 10d, 12d, and 15d, the IC 50 values of which are 1.8, 3.3, and 3.6 lM, respectively. Structure-activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of para-benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of 10d, 12d, 15d, and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 10d and 15d with a-glucosidase.

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“…The molecular basis of the new inhibitors mainly relies on an α,β-unsaturated carbonyl function conjugated to an aromatic scaffold which confers complete electron delocalization to the molecule thus reducing its redox potential [42][43][44]. This geometric motif is highly susceptible to electron transfer reactions with the amino acid residues of the catalytic domain of tyrosinase and laccase proteins [45,46].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Studies of the Inhibitory Effect of Hydroxylated Phenylpropanoids and Biphenols Derivatives on Tyrosinase and Laccase Enzymes

et al. 2020

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The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cycles of mammals, insects and microorganisms. Investigation of inhibitors of these two enzymes may lead to the discovery of whitening agents, medicinal products, anti-browning substances and compounds for controlling harmful insects and bacteria. A small collection of novel reversible tyrosinase and laccase inhibitors with a phenylpropanoid and hydroxylated biphenyl core was prepared using naturally occurring compounds and their activity was measured by spectrophotometric and electrochemical assays. Biosensors based on tyrosinase and laccase enzymes were constructed and used to detect the type of protein-ligand interaction and half maximal inhibitory concentration (IC50). Most of the inhibitors showed an IC50 in a range of 20–423 nM for tyrosinase and 23–2619 nM for laccase. Due to the safety concerns of conventional tyrosinase and laccase inhibitors, the viability of the new compounds was assayed on PC12 cells, four of which showed a viability of roughly 80% at 40 µM. In silico studies on the crystal structure of laccase enzyme identified a hydroxylated biphenyl bearing a prenylated chain as the lead structure, which activated strong and effective interactions at the active site of the enzyme. These data were confirmed by in vivo experiments performed on the insect model Tenebrio molitur.

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Design, synthesis and evaluation of cinnamic acid ester derivatives as mushroom tyrosinase inhibitors

Cited by 38 publications

References 34 publications

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

Natural and Bioinspired Phenolic Compounds as Tyrosinase Inhibitors for the Treatment of Skin Hyperpigmentation: Recent Advances

Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives

Synthesis and Studies of the Inhibitory Effect of Hydroxylated Phenylpropanoids and Biphenols Derivatives on Tyrosinase and Laccase Enzymes

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