Inhibition of tyrosinase by 4<i>H</i>‐chromene analogs: Synthesis, kinetic studies, and computational analysis

Brasil, Edikarlos; Canavieira, Luciana M.; Cardoso, Érica T. C.; Silva, Edilene O.; Lameira, Jerônimo; Nascimento, José Luiz Martins do; Eifler‐Lima, Vera Lucia; Macchi, Barbarella de Matos; Sriram, Dharmarajan; Bernhardt, Paul V.; Silva, José Rogério A.; Williams, Craig M.; Alves, Cláudio Nahum

doi:10.1111/cbdd.13001

Cited by 19 publications

(17 citation statements)

References 38 publications

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“…The identified residues have been reported to be important for stabilizing the interactions of the derivatives with the active site [ 12 ]. Furthermore, the formation of hydrogen bonds with the residues Met215, Asn205, and Glu195 have been shown to be relevant for the molecular recognition and stabilization of the interactions with the binding pocket [ 64 , 65 ].…”

Section: Resultsmentioning

confidence: 99%

“…The molecular docking results showed that the KA derivatives [ 65 ] have a high conformational selectivity to the tyrosinase when compared with kojic acid, mainly due to the presence of a substituted phenyl group, which formed new interactions with the residues of the binding pocket. All derivatives showed favorable interactions that are consistent with the chelation of copper ions (Cu-A and Cu-B) ( Table S3 ).…”

Section: Resultsmentioning

confidence: 99%

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Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

et al. 2021

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Tyrosinases belong to the functional copper-containing proteins family, and their structure contains two copper atoms, in the active site, which are coordinated by three histidine residues. The biosynthesis of melanin in melanocytes has two stages depending on the actions of the natural substrates L-DOPA and L-tyrosine. The dysregulation of tyrosinase is involved in skin cancer initiation. In the present study, using molecular modeling tools, we analyzed the inhibition activity of tyrosinase activity using kojic acid (KA) derivatives designed from aromatic aldehydes and malononitrile. All derivatives showed conformational affinity to the enzyme active site, and a favorable distance to chelate the copper ion, which is essential for enzyme function. Molecular dynamics simulations revealed that the derivatives formed promising complexes, presenting stable conformations with deviations between 0.2 and 0.35 Å. In addition, the investigated KA derivatives showed favorable binding free energies. The most stable KA derivatives showed the following binding free energies: −17.65 kcal mol−1 (D6), −18.07 kcal mol−1 (D2), −18.13 (D5) kcal mol−1, and −10.31 kcal mol−1 (D4). Our results suggest that these derivatives could be potent competitive inhibitors of the natural substrates of L-DOPA (−12.84 kcal mol−1) and L-tyrosine (−9.04 kcal mol−1) in melanogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

et al. 2021

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“…The interaction mode of the various pigments into the binding pockets of mTYR and hTYRP1 was also assessed by a molecular docking study. This computational technique has been successfully used to predict the binding of potential inhibitors to tyrosinase en zymes [38][39][40][41][42]. To validate the docking protocol, the crystallographic inhibitor tropolone was re-docked.…”

Section: Molecular Dockingmentioning

confidence: 99%

The Role of Anthocyanins, Deoxyanthocyanins and Pyranoanthocyanins on the Modulation of Tyrosinase Activity: An In Vitro and In Silico Approach

Correia

Oliveira

Araújo

et al. 2021

IJMS

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Tyrosinase is the central enzyme involved in the highly complex process of melanin formation, catalyzing the rate-limiting steps of this biosynthetic pathway. Due to such a preponderant role, it has become a major target in the treatment of undesired skin pigmentation conditions and also in the prevention of enzymatic food browning. Numerous phenolic-based structures from natural sources have been pointed out as potential tyrosinase inhibitors, including anthocyanins. The aim of the present study was to individually assess the tyrosinase inhibitory activity of eight purified compounds with a variable degree of structural complexity: native anthocyanins, deoxyanthocyanins, and pyranoanthocyanins. The latter two, the groups of anthocyanin-related compounds with enhanced stability, were tested for the first time. Compounds 1 to 4 (luteolinidin, deoxymalvidin, cyanidin-, and malvidin-3-O-glucoside) revealed to be the most effective inhibitors, and further kinetic studies suggested their inhibition mechanism to be of a competitive nature. Structure–activity relationships were proposed based on molecular docking studies conducted with mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (hTYRP1) crystal structures, providing information about the binding affinity and the different types of interactions established with the enzyme’s active center which corroborated the findings of the inhibition and kinetic studies. Overall, these results support the applicability of these compounds as pigmentation modulators.

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“…This residue corresponds to Asn364 of TYR and interacts with KA and CA in a similar manner. Val283 has been discussed before to form π–π stacking interactions with ligands [ 49 , 56 ], and this is also true for Val377 in TYR. Other similar interactions can be noticed for Phe90, Ala287, and Phe292 of abTYR and Phe207, Ser380, and Phe386 of TYR ( Figure S5 ).…”

Section: Resultsmentioning

confidence: 99%

Theoretical Studies of Cyanophycin Dipeptides as Inhibitors of Tyrosinases

Krzemińska

Kwiatos

Soares

et al. 2022

IJMS

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The three-dimensional structure of tyrosinase has been crystallized from many species but not from Homo sapiens. Tyrosinase is a key enzyme in melanin biosynthesis, being an important target for melanoma and skin-whitening cosmetics. Several studies employed the structure of tyrosinase from Agaricus bisporus as a model enzyme. Recently, 98% of human genome proteins were elucidated by AlphaFold. Herein, the AlphaFold structure of human tyrosinase and the previous model were compared. Moreover, tyrosinase-related proteins 1 and 2 were included, along with inhibition studies employing kojic and cinnamic acids. Peptides are widely studied for their inhibitory activity of skin-related enzymes. Cyanophycin is an amino acid polymer produced by cyanobacteria and is built of aspartic acid and arginine; arginine can be also replaced by other amino acids. A new set of cyanophycin-derived dipeptides was evaluated as potential inhibitors. Aspartate–glutamate showed the strongest interaction and was chosen as a leading compound for future studies.

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Inhibition of tyrosinase by 4H‐chromene analogs: Synthesis, kinetic studies, and computational analysis

Cited by 19 publications

References 38 publications

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

The Role of Anthocyanins, Deoxyanthocyanins and Pyranoanthocyanins on the Modulation of Tyrosinase Activity: An In Vitro and In Silico Approach

Theoretical Studies of Cyanophycin Dipeptides as Inhibitors of Tyrosinases

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