Comprehensive kinetic and structural studies of different flavonoids inhibiting diphenolase activity of mushroom tyrosinase

Gheibi, Nematollah; Zavareh, S. Hosseini; Behbahani, Golamreza Rezaei; Haghbeen, Kamahldin; Sabet, Mojgan; Ilghari, Dariush; Chegini, Koorosh Goodarzvand

doi:10.1134/s0003683816030054

Cited by 11 publications

(14 citation statements)

References 25 publications

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“…The type of inhibition proposed the coordination of these compounds with the copper clusters of enzyme active sites. The lower K i of complexes I and II in comparison with chrysin ( K i = 0.79 and IC 50 = 1.45 mM) and LA and ALA ( K i = 0.53; IC 50 = 0.97 mM and K i = 0.34; IC 50 = 0.63 mM, respectively; data not published) confirm that their esterification produced stronger inhibitors of MT (Gheibi et al, ).…”

Section: Resultsmentioning

confidence: 82%

“…Kinetics data from previous studies clearly show that flavonoid derivatives reversibly block the catecholase activity of MT with inhibitory potencies in the following order: chrysin < quercetin < naringin < Gallic acid. Nonetheless, these structurally similar substances inhibit enzyme activity through different mechanisms (Gheibi et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…The diphenolase activity of MT was measured by the oxidation reaction of L‐DOPA to DOPA‐quinone at 475 nm (dopachrome accumulation wavelength) at 25°C using the molar absorption coefficient of 3,700 M –1 cm –1 (Gheibi et al, ; Haghbeen et al, ). Absorption measurements were accomplished utilizing a UV‐2100 spectrophotometer (Rayleigh).…”

Section: Methodsmentioning

confidence: 99%

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Effect of chrysin omega‐3 and 6 fatty acid esters on mushroom tyrosinase activity, stability, and structure

et al. 2018

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The estreification of chrysin with α‐Linolenic acid (complex I) and linoleic acid (complex II) poly unsaturated fatty acids resulted to design of new mushroom tyrosinase (MT) inhibitors. Thermodynamic parameters of enzymes, including the melting point (Tm) and ∆G values, were obtained from thermal and chemical denaturation curves. Complexes I and II showed a competitive inhibitory effect on MT with Ki values of 0.45 and 0.29 mM, respectively. The Tm values were calculated as 328.6, 322.4, and 318 K and the ∆G values as 62.8, 52.9, and 47.1 KJ mol−1 for the enzyme alone and its interaction with complexes I and II, respectively. Intrinsic and extrinsic fluorescence techniques showed structural instability of the enzyme in concomitance with a decrease in the regular secondary structure acquired using CD spectrometry. This data clearly prove that the new derivatives show a stronger inhibitory effect than the separate compounds. Molecular docking analysis showed that the best possible interaction condition was achieved for chrysin with n‐6. Practical applications MT is a suitable model in medicine for the investigation of melanogenesis, skin disorders, and hyperpigmentation because of its accessibility and close structural similarity to mammalian tyrosinase. In recent years, the designing of tyrosinase inhibitors from natural substances for prevention of hyperpigmentation in medicine, skin cosmetics, and undesired browning in agriculture and food industry has risen sharply. Many of the pharmaceutical products based on the use of flavonoids and poly unsaturated acids as natural compounds or on their semi‐synthetic derivatives have been interested for investigations because of their usefulness in many pathological conditions such as inflammation, cancer, and skin disorders. The limitation of the flavonoids applications are low bioavailability, permeability, and solubility for the cells. In this study, conjugation of chrysin with n‐3 and n‐6 fatty acids resulted in a stronger inhibitors of MT with a synergic inhibitory effect on its activity.

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Section: Resultsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Effect of chrysin omega‐3 and 6 fatty acid esters on mushroom tyrosinase activity, stability, and structure

et al. 2018

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“…The deoxy type is similar to the met form but lacks the hydroxide bridges (Abdelrasool and Said, 2017;Chang, 2009;Choi et al, 2017). Importantly, this enzyme catalyzes the hydroxylation reactions, leading to the formation of melanin through 3,4-dihydroxyphenylalanine (L-DOPA) and L-DOPA-quinone (Gheibi et al, 2016). Quinines can react with proteins and amino acids to form black or brown products (Sugumaran and Barek, 2016) or evolve chemically to form polyphenolic compounds or melanin (Gheibi et al, 2016;Ullah et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, this enzyme catalyzes the hydroxylation reactions, leading to the formation of melanin through 3,4-dihydroxyphenylalanine (L-DOPA) and L-DOPA-quinone (Gheibi et al, 2016). Quinines can react with proteins and amino acids to form black or brown products (Sugumaran and Barek, 2016) or evolve chemically to form polyphenolic compounds or melanin (Gheibi et al, 2016;Ullah et al, 2016). Moreover, tyrosinase plays a key role in different processes such as melanin production in the skin, wound healing, agriculture, and cosmetic industry (Choi and Shin, 2016;Popoola et al, 2015;Taherkhani and Gheibi, 2014).…”

Section: Introductionmentioning

confidence: 99%

In silico assessment of the inhibitory effect of four flavonoids (Chrysin, Naringin, Quercetin, Kaempferol) on tyrosinase activity using the MD simulation approach

Farasat

Ghorbani

Gheibi

et al. 2020

bta

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Tyrosinase is a tetrameric enzyme that plays an important role in pigment production. Overproduction of melanin, which may lead to several skin disorders, is a result of tyrosinase activity. Hence, tyrosinase inhibitors are of key importance in the treatment of these disorders. In the present study, four flavonoid inhibitors, namely chrysin, naringin, quercetin, and kaempferol, were evaluated physiochemically, and the inhibitory effects of these compounds on tyrosinase activity were evaluated using the molecular dynamics (MD) simulation method. To create the best conformation of the enzyme-substrate/inhibitor, the docking process for enzyme-substrate, i.e., enzymechrysin, enzyme-quercetin, enzyme-naringin, and enzyme-kaempferol, was performed. The complexes with the best binding energies were selected as the models for the MD simulation process. Furthermore, the structural (RMSD, Rg, RMSF, and Distance) and the thermodynamics properties of the complexes were evaluated. Additionally, the PMF was conducted to calculate the binding free energies. The results showed that chrysin, quercetin and the substrate were at similar distances to the amino acids of the active site, but naringin and kaempferol were closer to the active site of the enzyme than the substrate. Moreover, the analysis of the binding energy revealed that the substrates, chrysin, kaempferol, quercetin, and naringin bound to the enzyme with binding energies of !7.8, !3.1, !7.1, !3.9, and !8.4 kcal/mol, respectively, which confirms that naringin has the highest inhibitory effect on tyrosinase among other inhibitors, which makes it an appropriate candidate as a whitening agent in skin disorders.

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Exploring the Potential of ω3 Derivatives as Tyrosinase Inhibitors: A Comprehensive Study Combining Experimental, Computational, and Biological Approaches

et al. 2023

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In this work, the inhibitory ability and mechanism of ω3nicotinic acid (ω3-NA) and ω3-Picolinic acid (ω3-PA) complexes on the activity of mushroom tyrosinase (MT) were scrutinized for progressing a novel MT inhibitor. The complexes were synthesized. It was shown to have a considerable inhibition on the MT activity and K i value of ω3-NA and ω3-PA on MT equal to 5.2 and 5.1 mM, respectively. ω3-NA and ω3-PA inhibited MT with V max values in the range of 0.134 mM and 0.14 mM, respectively. The outputs obtained from fluorescence quenching specified that ω3-NA and ω3-PA could interact with MT.Especially, the decrease in fluorescence intensity was due to the formation of a ligand-enzyme complex which was mostly motivated by hydrogen bonding and hydrophobic forces. The presence of ω3-NA and ω3-PA altered the structure of MT and reduced the α-helix of the enzyme. Molecular docking investigation along with molecular dynamics simulation exhibited that ligands-MT formation is directed by hydrogen binding with Trp136, His263, and Val299 residues. The results highlight that ω3-NA and ω3-PA can be considered as possible inhibitors in treating hyperpigmentation via MT enzyme inhibition. Results and DiscussionAnalysis of complexes synthesized by NMR Synthesis confirmation and characterization were performed using NMR. 13 C spectra were taken from the synthesized compounds. The 1 H and 13 C NMR ω3-NA showed the shifting 14.1 (CH 3 ), 21.2 (2CH 2 ), 22.8 (CH 2 ), 26.1 (3CH 2 ), 30 (CH 2 ), 31

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Comprehensive kinetic and structural studies of different flavonoids inhibiting diphenolase activity of mushroom tyrosinase

Cited by 11 publications

References 25 publications

Effect of chrysin omega‐3 and 6 fatty acid esters on mushroom tyrosinase activity, stability, and structure

Effect of chrysin omega‐3 and 6 fatty acid esters on mushroom tyrosinase activity, stability, and structure

In silico assessment of the inhibitory effect of four flavonoids (Chrysin, Naringin, Quercetin, Kaempferol) on tyrosinase activity using the MD simulation approach

Exploring the Potential of ω3 Derivatives as Tyrosinase Inhibitors: A Comprehensive Study Combining Experimental, Computational, and Biological Approaches

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