Plants as a Promising Reservoir of Tyrosinase Inhibitors

2020 ◽  
Vol 17 ◽  
Author(s):  
Rabia Riaz ◽  
Paolo Zucca ◽  
Antonio Rescigno ◽  
Stefania Peddio ◽  
Rahman Shah Zaib Saleem ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Secondary Metabolites ◽  
Biosynthetic Pathway ◽  
Kojic Acid ◽  
Structure Optimization ◽  
Tyrosinase Activity ◽  
Plant Origin ◽  
Current Review ◽  
Tyrosinase Inhibitors ◽  
Mechanistic Investigations

Abstract:: The process of melanogenesis, that takes place in the melanocytes of the epidermis, leads to hyperpigmentation. The biosynthetic pathway for production of melanin involves the enzyme tyrosinase that has been an attractive target for cosmaceutical research. Numerous synthetic, semisynthetic and natural, especially plant-based, inhibitors of tyrosinase have been reported in the literature. In plants, the secondary metabolites like flavonoids, chalcones, stilbenes, tannins, hydroquinone and kojic acid, etc... have been shown to possess the anti-tyrosinase activity. In the current review, we have covered the progress in this sphere that would be useful for not only further mechanistic investigations but also for the optimization of the structure of the metabolites for improved activity and selectivity. Thus the review presents a comprehensive report on tyrosinase inhibitors of plant origin reported in the extract form or as isolated compounds. Huge gap has been found between research and industry due to inconsistent pursual of the potent plant based extracts. There is a need to completely evaluate the extracts for structure optimization using molecular docking and evaluation of the safety inorder to benefit the industry with non toxic biological friendly products through invivo and exvivo optimization.

Evaluation of Cytotoxic and Tyrosinase Inhibitory Activities of 2-phenoxy(thiomethyl) pyridotriazolopyrimidines: In Vitro and Molecular Docking Studies

2020 ◽  
Vol 20 (14) ◽  
pp. 1714-1721
Author(s):  
Hatem A. Abuelizz ◽  
El Hassane Anouar ◽  
Mohamed Marzouk ◽  
Mizaton H. Hasan ◽  
Siti R. Saleh ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Kojic Acid ◽  
Docking Studies ◽  
Breast Adenocarcinoma ◽  
Amino Acid Residues ◽  
New Class ◽  
Structure Activity ◽  
Tyrosinase Inhibitors ◽  
Mcf 7

Background: The use of tyrosinase has confirmed to be the best means of recognizing safe, effective, and potent tyrosinase inhibitors for whitening skin. Twenty-four 2-phenoxy(thiomethyl)pyridotriazolopyrimidines were synthesized and characterized in our previous studies. Objective: The present work aimed to evaluate their cytotoxicity against HepG2 (hepatocellular carcinoma), A549 (pulmonary adenocarcinoma), MCF-7 (breast adenocarcinoma) and WRL 68 (embryonic liver) cell lines. Methods: MTT assay was employed to investigate the cytotoxicity, and a tyrosinase inhibitor screening kit was used to evaluate the Tyrosinase (TYR) inhibitory activity of the targets. Results: The tested compounds exhibited no considerable cytotoxicity, and nine of them were selected for a tyrosinase inhibitory test. Compounds 2b, 2m, and 5a showed good inhibitory percentages against TYR compared to that of kojic acid (reference substance). Molecular docking was performed to rationalize the Structure-Activity Relationship (SAR) of the target pyridotriazolopyrimidines and analyze the binding between the docked-selected compounds and the amino acid residues in the active site of tyrosinase. Conclusion: The target pyridotriazolopyrimidines were identified as a new class of tyrosinase inhibitors.

scholarly journals Electrochemical Screening and Evaluation of Lamiaceae Plant Species from South Africa with Potential Tyrosinase Activity

Sensors ◽  
2019 ◽  
Vol 19 (5) ◽  
pp. 1035 ◽  
Author(s):  
Ninon Etsassala ◽  
Tesfaye Waryo ◽  
Olugbenga Popoola ◽  
Adewale Adeloye ◽  
Emmanuel Iwuoha ◽  
...  
Keyword(s):  
South Africa ◽  
South African ◽  
Kojic Acid ◽  
Screening Method ◽  
Tyrosinase Activity ◽  
Minimum Concentration ◽  
Methanolic Extracts ◽  
Fast Screening ◽  
African Flora ◽  
Tyrosinase Inhibitors

South Africa is a country with a wide variety of plants that may contain excellent anti-tyrosinase inhibitors. With wide applications in cosmetics, pharmaceuticals and food products, tyrosinase inhibitors have received very special attention in the recent past as a way of preventing the overproduction of melanin in epidermal layers which often over time brings detrimental effects on human skin. In this present study, a fast screening method using a cyclic voltammetry technique was applied in the evaluation of methanolic extracts of twenty-five species of plants from the Lamiaceae family for anti-tyrosinase activity. Among these plants, those that showed a fast current inhibition rate at a minimum concentration when compared to a kojic acid standard were classified as having the greatest anti-tyrosinase activity. These include Salvia chamelaeagnea, S. dolomitica, Plectranthus ecklonii, P. namaensis, and P. zuluensis. The results presented herein focused in particular on providng firsthand information for further extensive research and exploration of natural product materials with anti-tyrosinase activity from South African flora for use in cosmetics, skin care and medicinal treatments.

scholarly journals Novel Anti-Melanogenic Compounds, (Z)-5-(Substituted Benzylidene)-4-thioxothiazolidin-2-one Derivatives: In Vitro and In Silico Insights

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4963
Author(s):  
Heejeong Choi ◽  
Il Young Ryu ◽  
Inkyu Choi ◽  
Sultan Ullah ◽  
Hee Jin Jung ◽  
...  
Keyword(s):  
Active Site ◽  
Kojic Acid ◽  
Docking Simulation ◽  
Tyrosinase Activity ◽  
In Vitro Assays ◽  
Mushroom Tyrosinase ◽  
Tyrosinase Inhibitors ◽  
Melanin Contents ◽  
Human Tyrosinase

To confirm that the β-phenyl-α,β-unsaturated thiocarbonyl (PUSTC) scaffold, similar to the β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold, acts as a core inhibitory structure for tyrosinase, twelve (Z)-5-(substituted benzylidene)-4-thioxothiazolidin-2-one ((Z)-BTTZ) derivatives were designed and synthesized. Seven of the twelve derivatives showed stronger inhibitory activity than kojic acid against mushroom tyrosinase. Compound 2b (IC50 = 0.47 ± 0.97 µM) exerted a 141-fold higher inhibitory potency than kojic acid. Kinetic studies’ results confirmed that compounds 2b and 2f are competitive tyrosinase inhibitors, which was supported by high binding affinities with the active site of tyrosinase by docking simulation. Docking results using a human tyrosinase homology model indicated that 2b and 2f might potently inhibit human tyrosinase. In vitro assays of 2b and 2f were conducted using B16F10 melanoma cells. Compounds 2b and 2f significantly and concentration-dependently inhibited intracellular melanin contents, and the anti-melanogenic effects of 2b at 10 µM and 2f at 25 µM were considerably greater than the inhibitory effect of kojic acid at 25 µM. Compounds 2b and 2f similarly inhibited cellular tyrosinase activity and melanin contents, indicating that the anti-melanogenic effects of both were due to tyrosinase inhibition. A strong binding affinity with the active site of tyrosinase and potent inhibitions of mushroom tyrosinase, cellular tyrosinase activity, and melanin generation in B16F10 cells indicates the PUSTC scaffold offers an attractive platform for the development of novel tyrosinase inhibitors.

scholarly journals Inhibitory and Acceleratory Effects ofInonotus obliquuson Tyrosinase Activity and Melanin Formation in B16 Melanoma Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Zheng-Fei Yan ◽  
Yang Yang ◽  
Feng-Hua Tian ◽  
Xin-Xin Mao ◽  
Yu Li ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Therapeutic Agent ◽  
Kojic Acid ◽  
Ethyl Acetate Extract ◽  
Tyrosinase Activity ◽  
Mushroom Tyrosinase ◽  
Melanin Content ◽  
Inonotus Obliquus ◽  
Nmr Data ◽  
Tyrosinase Inhibitors

The aim of the present study is to preliminarily investigate the antimelanogenesis effect ofInonotus obliquusextracts by cell-free mushroom tyrosinase assay. It was found that petroleum ether and n-butanol extracts might contain unknown potential tyrosinase inhibitors, while its ethyl acetate extract might contain some unknown accelerators. Six compounds were isolated and their structures were identified by interpretation of NMR data and nicotinic acid was first discovered inInonotus obliquus. In cells testing, betulin and trametenolic acid decreased tyrosinase activity and melanin content, while inotodiol and lanosterol significantly increased tyrosinase activity and melanin content, showing anAC⁡50of 9.74 and 8.43 μM, respectively. Nicotinie acid, 3β,22,25-trihydroxy-lanosta-8-ene, had a little or no effect on tyrosinase. Betulin exhibited a mode of noncompetitive inhibition with aKI=KISof 0.4 μM on tyrosinase activity showing an IC50of 5.13 μM and being more effective than kojic acid (6.43 μM), and trametenolic acid exhibited a mode of mixed inhibition with aKIof 0.9 μM,KISof 0.5 μM, and anIC50of 7.25 μM. We proposed betulin and trametenolic acid as a new candidate of potent tyrosinase inhibitors and inotodiol and lanosterol as accelerators that could be used as therapeutic agent.

scholarly journals Enzyme-Site Blocking Combined with Optimization of Molecular Docking for Efficient Discovery of Potential Tyrosinase Specific Inhibitors from Puerariae lobatae Radix

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2612 ◽  
Author(s):  
Haichun Liu ◽  
Yitian Zhu ◽  
Ting Wang ◽  
Jin Qi ◽  
Xuming Liu
Keyword(s):  
Molecular Docking ◽  
Structural Modification ◽  
Enzyme Inhibitors ◽  
Kojic Acid ◽  
Systematic Evaluation ◽  
Tyrosinase Inhibition ◽  
Computational Docking ◽  
Site Blocking ◽  
Leading Compounds ◽  
Positive Results

Enzyme inhibitors from natural products are becoming an attractive target for drug discovery and development; however, separating enzyme inhibitors from natural-product extracts is highly complex. In this study, we developed a strategy based on tyrosinase-site blocking ultrafiltration integrated with HPLC-QTOF-MS/MS and optimized molecular docking to screen tyrosinase inhibitors from Puerariae lobatae Radix extract. Under optimized ultrafiltration parameters, we previously used kojic acid, a known tyrosinase inhibitor, to block the tyrosinase active site in order to eliminate false-positive results. Using this strategy, puerarin, mirificin, daidzin and genistinc were successfully identified as potential ligands, and after systematic evaluation by several docking programs, the rank of the identified compounds predicted by computational docking was puerarin > mirificin > kojic acid > daidzin ≈ genistin, which agreed with the results of tyrosinase-inhibition assays. Structure-activity relationships indicated that C-glycosides showed better tyrosinase inhibition as compared with O-glycosides, with reduced inhibition achieved through the addition of glycosyl, which provides ideas about the screen of leading compounds and structural modification.

scholarly journals Synthesis of Novel Compounds as New Potent Tyrosinase Inhibitors

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hooshang Hamidian
Keyword(s):  
Kojic Acid ◽  
Azo Compounds ◽  
The Novel ◽  
Mushroom Tyrosinase ◽  
Reference Standard ◽  
Tyrosinase Inhibition ◽  
H Nmr ◽  
Ft Ir ◽  
Tyrosinase Inhibitors ◽  
C Nmr

In the present paper, we report the synthesis and pharmacological evaluation of a new series of azo compounds with different groups (1-naphthol, 2-naphthol, andN,N-dimethylaniline) and trifluoromethoxy and fluoro substituents in the scaffold. All synthesized compounds (5a–5f) showed the most potent mushroom tyrosinase inhibition (IC50values in the range of 4.39 ± 0.76–1.71 ± 0.49 µM), comparable to the kojic acid, as reference standard inhibitor. All the novel compounds were characterized by FT-IR,1H NMR,13C NMR, and elemental analysis.

scholarly journals The fungal gene cluster for biosynthesis of the antibacterial agent viriditoxin

2019 ◽  
Author(s):  
Andrew S. Urquhart ◽  
Jinyu Hu ◽  
Yit-Heng Chooi ◽  
Alexander Idnurm
Keyword(s):  
Secondary Metabolites ◽  
Gene Cluster ◽  
Gene Disruption ◽  
Biosynthetic Pathway ◽  
Fluorescent Protein ◽  
Model Species ◽  
Paecilomyces Variotii ◽  
Bioinformatic Approaches ◽  
Green Fluorescent ◽  
Fungal Gene

AbstractBackgroundViriditoxin is one of the ‘classical’ secondary metabolites produced by fungi and that has antibacterial and other activities; however, the mechanism of its biosynthesis has remained unknown.ResultsHere, a gene cluster responsible for its synthesis was identified, using bioinformatic approaches from two species that produce viriditoxin and then through gene disruption and metabolite profiling. All eight genes in the cluster inPaecilomyces variotiiwere mutated, revealing their roles in the synthesis of this molecule and establishing its biosynthetic pathway which includes an interesting Baeyer-Villiger monooxygenase catalyzed reaction. Additionally, a candidate catalytically-inactive hydrolase was identified as being required for the stereoselective biosynthesis of (M)-viriditoxin. The localization of two proteins were assessed by fusing these proteins to green fluorescent protein, revealing that at least two intracellular structures are involved in the compartmentalization of the synthesis steps of this metabolite.ConclusionsThe full pathway for synthesis of viriditoxin was established by a combination of genomics, bioinformatics, gene disruption and chemical analysis processes. Hence, this work reveals the basis for the synthesis of an understudied class of fungal secondary metabolites and provides a new model species for understanding the synthesis of biaryl compounds with a chiral axis.

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