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.

Synergistic Effects of Linderanolide B Combined with Arbutin, PTU or Kojic Acid on Tyrosinase Inhibition

2015 ◽  
Vol 16 (12) ◽  
pp. 1120-1126 ◽  
Author(s):  
You-Cheng Hseu ◽  
Kuo-Chen Cheng ◽  
Yi-Chieh Lin ◽  
Chung-Yi Chen ◽  
Hsin-Yu Chou ◽  
...  
Keyword(s):  
Kojic Acid ◽  
Synergistic Effects ◽  
Tyrosinase Inhibition

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.

Selection of oxypeucedanin as a potential antagonist from molecular docking analysis of HSP90

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Joshua Oluwasegun Bamidele ◽  
George Oche Ambrose ◽  
Oluwaseun Suleiman Alakanse
Keyword(s):  
Molecular Docking ◽  
Liver Toxicity ◽  
Docking Study ◽  
Docking Studies ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Computational Docking ◽  
Drug Candidates ◽  
Expression Rate ◽  
Client Proteins

AbstractHSP90 is observed as one of the copious molecular chaperones that play a key role in mediating appropriate folding, maturation, and firmness of many client proteins in cells. The expression rate of HSP90 in cancer cells is at a level of 2- to 10-fold higher than the 1- to 2-fold of its unstressed and healthy ones. To combat this, several inhibitors to HSP90 protein have been studied (such as geldanamycin and its derivative 17-AAG and 17-DMAG) and have shown some primary side effects including plague, nausea, vomiting, and liver toxicity, hence the search for the best-in-class inhibitor for this protein through in silico. This study is aimed at analyzing the inhibitory potency of oxypeucedanin-a furocoumarin derivations, which have been reported to have antipoliferative activity in human prostrate carcinoma DN145 cells, and three other drug candidates retrieved from the literature via computational docking studies. The results showed oxypeucedanin as the compound with the highest binding energy of −9.2 kcal/mol. The molecular docking study was carried out using PyRx, Auto Dock Vina option, and the target was validated to confirm the proper target and the docking procedure employed for this study.

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 Splash mask formulation of tangerine (Citrus reticulata Blanco.) peel extract and turmeric (Curcuma longa L) extract as a whitening agent

2020 ◽  
Vol 6 (3) ◽  
pp. 341
Author(s):  
Framesti Frisma Sriarumtias ◽  
Nurul Auliasari
Keyword(s):  
Kojic Acid ◽  
Curcuma Longa ◽  
Citrus Reticulata ◽  
Tyrosinase Inhibition ◽  
Elisa Method ◽  
Tropical Country ◽  
Citrus Reticulata Blanco ◽  
Whitening Agent ◽  
Tyrosinase Enzyme ◽  
Peel Extract

<p class="abstract"><strong>Background:</strong> Indonesia is a tropical country that is exposed to the sun for 12 hours, one of the harm effects of sunlight which is damage to the skin. The purpose of this study was to determine tyrosinase inhibition of tangerin peel extract (<em>Citrus reticulata Blanco</em>.) from Garut, West Java, Indonesia then develop the splash mask from the extract.</p><p class="abstract"><strong>Methods:</strong> The tangerine peel will be extracted by maceration method. The splash mask formulation containing tangerine peel extract which has a whitening agent. Tyrosinase inhibition determine by ELISA method with tyrosinase enzyme and L-DOPA substrat.<strong></strong></p><p class="abstract"><strong>Results:</strong> The results showed that tangerine peel extract had tyrosinase inhibition with the IC50 of 30.000 ppm, which has less effective than kojic acid with IC50 81,10 ppm. Splash mask containing of 1000x IC50, evaluation carried out for 28 days showed that preparations made pharmaceutically stable.</p><p class="abstract"><strong>Conclusions:</strong> In addition, the whitening agent of tangerine peel extract is in the weak category. It is hoped that this research can increase the value of tangerine peel waste.</p><p> </p>

scholarly journals Tel-Cu-NPs Catalyst: Synthesis of Naphtho[2,3-g]phthalazine Derivatives as Potential Inhibiters of Tyrosinase Enzymes and Their Investigation in Kinetic, Molecular Docking, and Cytotoxicity Studies

Catalysts ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1442
Author(s):  
Keerthana Selvaraj ◽  
Ali Daoud ◽  
Saud Alarifi ◽  
Akbar Idhayadhulla
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Kojic Acid ◽  
Docking Studies ◽  
Kinetic Behavior ◽  
One Pot ◽  
Catalyst Synthesis ◽  
Cytotoxicity Activity ◽  
Cytotoxicity Studies ◽  
High Yields

Novel one-pot synthesis naphtho[2,3-g]phthalazine (1a–1k) of Mannich base derivatives can be achieved via grindstone chemistry using a Tel-Cu-NPs (telmisartan-copper nanoparticles) catalyst. This method offers efficient mild reaction conditions and high yields. Tyrosinase inhibitory activity was evaluated for all synthesized compounds, along with analysis of kinetic behavior and molecular docking studies. The synthesized compound, 1c was (IC50 = 11.5 µM) more active than kojic acid (IC50 = 78.0 µM). Lineweaver Burk plots were used to analyze the kinetic behavior of the most active compound 1c, it was reversible and competitive behavior. Compound 1c and kojic acid occurred in the presence of 2-hydroxyketone, which has the same inhibitory mechanism. The molecular docking of compound 1c and the control kojic acid were docked against 2Y9X protein via the Schrodinger Suite. The compound 1c showed a respectable dock score (−5.6 kcal/mol) compared to kojic acid with a dock score of (−5.2 kcal/mol) in the 2Y9X protein. Cytotoxicity activity was also evaluated by using HepG2 (liver), MCF-7 (breast), and HeLa (cervical) cancer cell lines, and high activity for 1c (GI50 = 0.01, 0.03, and 0.04 µM, respectively) against all cell lines was found compared to standard and other compounds. Therefore, this study succeeded in testing a few promising molecules as potential antityrosinase agents.

Novel benzothiazole hydrazine carboxamide hybrid scaffolds as potential in vitro GABA AT enzyme inhibitors: Synthesis, molecular docking and antiepileptic evaluation

2019 ◽  
Vol 29 (14) ◽  
pp. 1825-1830
Author(s):  
Sadaf Jamal Gilani ◽  
Mohd. Zaheen Hassan ◽  
Syed Sarim Imam ◽  
Chandra Kala ◽  
Surya Prakash Dixit
Keyword(s):  
Molecular Docking ◽  
Enzyme Inhibitors ◽  
Hybrid Scaffolds

scholarly journals THE RECENT UPDATE OF DEOXYARBUTIN: A SKIN DEPIGMENTATION AGENT WITH TYROSINASE INHIBITION TARGETING

2020 ◽  
pp. 1-7
Author(s):  
MUCHTARIDI MUCHTARIDI ◽  
MENTARI LUTHFIKA DEWI
Keyword(s):  
Kojic Acid ◽  
Enzyme Inhibitor ◽  
Clinical Manifestations ◽  
Tyrosinase Inhibitor ◽  
Tyrosinase Inhibition ◽  
Considerable Potential ◽  
Abnormal Accumulation ◽  
Tyrosinase Enzyme ◽  
The Stability ◽  
Further Development

Melanin is produced through the process of melanogenesis, which serves to protect the skin from the damaging effects of UV radiation. Abnormal accumulation of melanin will aesthetically disturb even interfere with health. One of the clinical manifestations of abnormal accumulation of melanin is the incidence of melasma. Some of the tyrosinase enzyme inhibitor agents most widely used as Hydroquinone, Kojic acid and Arbutin do not give satisfactory results and cause serious side effects. Hydroquinone is known to cause ochronosis exogenous and cytotoxic. Kojic acid is known to cause allergies and mutagenic, while arbutinisis is known to have cytotoxic properties lower than hydroquinone, but less satisfactory depigmentation activity. There was a compound that has been synthesized by removing the hydroxy group of arbutin, known as deoxyarbutin (4-[Tetrahydro-2H-Pyrans-2-yl) oxy] phenol). Deoxyarbutin (dA) shows Ki 10-fold is lower than hydroquinone and 350-fold is lower than arbutin. IC50dA is 17.5+0.5 µmol/l, while the IC50 hydroquinone is 73.7+9.1 µmol/l. In terms of security, dA indicates that cell viability is 95% higher than hydroquinone. However, dA is thermolabile and photolabile. Several studies have shown satisfactory results to improve the stability of dA, that these compounds are considerable potential for further development as a depigmentation agent. The aim of this review is to describe how the potency of dA as a tyrosinase inhibitor interferes melanogenesis process through the latest depigmentation agent, its safety, efficacy and stability.

scholarly journals Potent Microbial and Tyrosinase Inhibitors from Stem Bark of Bauhinia Rufescens (Fabaceae)

2013 ◽  
Vol 8 (10) ◽  
pp. 1934578X1300801 ◽  
Author(s):  
Aminu Muhammad ◽  
Hasnah Mohd Sirat
Keyword(s):  
Kojic Acid ◽  
Stem Bark ◽  
Positive Control ◽  
Inhibition Assay ◽  
Bacterial Strains ◽  
Tyrosinase Inhibition ◽  
Fungal Strains ◽  
Inhibition Concentration ◽  
Tyrosinase Enzyme ◽  
Antimicrobial Assay

The stem bark extracts of Bauhinia rufescens Lam. (Fabaceae) yielded 6-methoxy-7-methyl-8-hydroxydibenz[ b,f]oxepin, α-amyrin acetate, β-sitosterol 3- O-β-D-xylopyranoside, 4-(2′-Hydroxyphenethyl)-5-methoxy-2-methylphenol, menisdaurin and sequoyitol. Their structures were determined using spectroscopic methods and comparisons with the literature data. For the antimicrobial assay Gram-positive and Gram-negative bacterial and fungal strains were tested, while the tyrosinase inhibition assay utilized L-DOPA as a substrate for the tyrosinase enzyme. 6-Methoxy-7-methyl-8-hydroxydibenz[ b,f]oxepin, α-amyrin acetate, β-sitosterol 3- O-β-D-xylopyranoside, menisdaurin and sequoyitol showed weak to moderate activities with minimum inhibition concentration (MIC) values in the range of 112.5–900 μg/mL against all bacterial strains, while the MIC values for the fungal strains were in the range of 28.1–450 μg/mL. In the tyrosinase inhibition assay, α-amyrin acetate was found to be moderately active against tyrosinase with an inhibition of 62% at 0.1 mg/mL. This activity was lower than that of the positive control, kojic acid (85%).

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