A new insight into mushroom tyrosinase inhibitors: docking, pharmacophore-based virtual screening, and molecular modeling studies

  title={A new insight into mushroom tyrosinase inhibitors: docking, pharmacophore-based virtual screening, and molecular modeling studies},
  author={Kowsar Bagherzadeh and Faezeh Shirgahi Talari and Amirhossein Sharifi and Mohammad Reza Ganjali and Ali Akbar Saboury and Massoud Amanlou},
  journal={Journal of Biomolecular Structure and Dynamics},
  pages={487 - 501}
Tyrosinase, a widely spread enzyme in micro-organisms, animals, and plants, participates in two rate-limiting steps in melanin formation pathway which is responsible for skin protection against UV lights’ harm whose functional deficiency result in serious dermatological diseases. This enzyme seems to be responsible for neuromelanin formation in human brain as well. In plants, the enzyme leads the browning pathway which is commonly observed in injured tissues that is economically very… 
Structure and inhibition mechanism of some synthetic compounds and phenolic derivatives as tyrosinase inhibitors: review and new insight.
  • Morteza Vaezi
  • Chemistry, Biology
    Journal of biomolecular structure & dynamics
  • 2022
The present review focuses on the recent and efficient tyrosinase inhibitors discovered from both synthetic sources and synthesized phenolic compounds, including flavonoid, carvacrol, thymol, cinnamic acid and resorcinol derivatives, and confirmed that understanding structural modification of inhibitors is a key role in finding novel and efficacious tyrosine inhibitors.
Novel amide derivatives as potent tyrosinase inhibitors; in-vitro, in-vivo antimelanogenic activity and computational studies.
Compound 5c is proposed as a potential candidate to control tyrosinase rooted hyperpigmentation in the future and demonstrates that 5c interact with copper ions and multiple amino acids in the active site of tyosinase with best glide score (-5.387 kcal/mol).
Glycosidic vs. Aglycol Form of Natural Products as Putative Tyrosinase Inhibitors
New potent natural inhibitors were retrieved from the ZINC database by the similarity-screening of 37 previously reported tyrosinase inhibitors by the results suggested that the glycosylated inhibitors could interact better with the enzyme than their aglycon forms.
Multifunctional Tyrosinase Inhibitor Peptides with Copper Chelating, UV-Absorption and Antioxidant Activities: Kinetic and Docking Studies
DIP1 was found to be the most potent tyrosinase inhibitor and the Lineweaver–Burk analysis demonstrated that DIP1 could be a multifunctional anti-tyrosinases agent with pharmaceutical and cosmeceutical applications.
Natural and synthetic flavonoid derivatives as new potential tyrosinase inhibitors: a systematic review
This review article is oriented to provide an insight and a deeper understanding of the tyrosinase inhibitory activity of an array of natural and bioinspired phenolic compounds with special emphasis on flavonoids to demonstrate how the position of ring substituents and their interaction with tyosinase could be correlated with their effectiveness or lack thereof against inhibiting the enzyme.
Prediction of new Hsp90 inhibitors based on 3,4-isoxazolediamide scaffold using QSAR study, molecular docking and molecular dynamic simulation
The QSAR and docking analyses shown to be beneficial tools in the proposal of anti-cancer activities and a leader to the synthesis of new Hsp90 inhibitors based 3,4-isoxazolediamide.
A novel method for explaining the product inhibition mechanisms via molecular docking: inhibition studies for tyrosinase from Agaricus bisporus.
It is suggested that the novel method used in this study to explain the inhibitory mechanism of l-cysteine may provide an affordable alternative to the expensive methods available for explaining the inhibitORY mechanism of TYR and those of other enzymes.
Computational approaches to predict binding interactions between mammalian tyrosinases and (S)-(+)-decursin and its analogues as potent inhibitors
The results showed that (S)-(+)-decursin and its analogues contain ester derivatives that interact with hydrophobic and aromatic residues, particularly Ile256 and Val265 in the binding site, which provides a foundation for the identification of new tyrosinase inhibitors for treating dermatological disorders.


Inhibition of mushroom tyrosinase by a newly synthesized ligand: inhibition kinetics and computational simulations
The inhibitory effect of a novel designed compound, 2-((1Z)-(2-(2,4-dinitrophenyl)hydrazin-1-ylidene)methyl)phenol, as a specific ligand which can bind to the copper ion of MT, has been assessed and molecular dynamics results show that ligand binds to the MT via both electrostatic and hydrophobic interactions with its different parts.
Tyrosinase inhibitors from natural and synthetic sources: structure, inhibition mechanism and perspective for the future
  • Y. Kim, H. Uyama
  • Chemistry, Medicine
    Cellular and Molecular Life Sciences CMLS
  • 2005
This article overviews the various inhibitors obtained from natural and synthetic sources with their industrial importance, and examines the role of tyrosinase in melanin biosynthesis and its role in dermatological disorders.
Structure-Based and Ligand-Based Drug Design for HER 2 Receptor
Both structure-based and ligand-based drug design were employed to design novel HER2 inhibitors from traditional Chinese medicine (TCM) using the HER2 structure model, which was built in homology modeling based on known receptors of the same family.
Crystal structure of Agaricus bisporus mushroom tyrosinase: identity of the tetramer subunits and interaction with tropolone.
The first structure of the full fungal tyrosinase complex from the mushroom Agaricus bisporus is presented, explaining how calcium ions stabilize the tetrameric state of the enzyme.
Molecular anatomy of tyrosinase and its related proteins: beyond the histidine-bound metal catalytic center.
The complete understanding of the Tyr copper-binding domain and the characterization of the residues determinant of the relative substrate affinities of the Tyrosinase related proteins (Tyrps) will improve the design of targeted mutagenesis experiments to understand the different catalytic capabilities of Tyr and Tyrps.
Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity
Resveratrol does not inhibit tyrosinase to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested.
Crystal structure of Manduca sexta prophenoloxidase provides insights into the mechanism of type 3 copper enzymes
The structure provides unique insights into the mechanism by which type 3 copper proteins differ in their enzymatic activities, albeit sharing a common active center, and a drastic change in electrostatic surface induced on cleavage at Arg-51 allows for localized PPO activation in insects.
Potential interaction of natural dietary bioactive compounds with COX-2.
Crystallographic Evidence That the Dinuclear Copper Center of Tyrosinase Is Flexible during Catalysis*
Crystal structures of copper-bound and metal-free tyrosinase in a complex with ORF378 designated as a “caddie” protein suggest that the caddie protein covers the hydrophobic molecular surface of tyosinase and interferes with the binding of a substrate tyrosine to the catalytic site of tyOSinase.