scholarly journals Inhibitory Effect of Phthalic Acid on Tyrosinase: The Mixed-Type Inhibition and Docking Simulations

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Shang-Jun Yin ◽  
Yue-Xiu Si ◽  
Guo-Ying Qian
Keyword(s):  
Phthalic Acid ◽  
Mixed Type ◽  
3D Structure ◽  
Computational Prediction ◽  
Inhibitory Effect ◽  
Binding Energies ◽  
Hydroxyl Groups ◽  
Tyrosinase Inhibition ◽  
Ans Binding ◽  
Docking Simulations

Tyrosinase inhibition studies are needed due to the medicinal applications such as hyperpigmentation. For probing effective inhibitors of tyrosinase, a combination of computational prediction and enzymatic assay via kinetics was important. We predicted the 3D structure of tyrosinase, used a docking algorithm to simulate binding between tyrosinase and phthalic acid (PA), and studied the reversible inhibition of tyrosinase by PA. PA inhibited tyrosinase in a mixed-type manner with a Ki=65.84±1.10 mM. Measurements of intrinsic and ANS-binding fluorescences showed that PA induced changes in the active site structure via indirect binding. Simulation was successful (binding energies for Dock6.3=-27.22 and AutoDock4.2=-0.97 kcal/mol), suggesting that PA interacts with LEU73 residue that is predicted commonly by both programs. The present study suggested that the strategy of predicting tyrosinase inhibition based on hydroxyl groups and orientation may prove useful for screening of potential tyrosinase inhibitors.

scholarly journals Urolithin and Reduced Urolithin Derivatives as Potent Inhibitors of Tyrosinase and Melanogenesis: Importance of the 4-Substituted Resorcinol Moiety

2021 ◽  
Vol 22 (11) ◽  
pp. 5616
Author(s):  
Sanggwon Lee ◽  
Heejeong Choi ◽  
Yujin Park ◽  
Hee Jin Jung ◽  
Sultan Ullah ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Phenyl Group ◽  
Homology Model ◽  
Hydroxyl Groups ◽  
Binding Affinities ◽  
Tyrosinase Inhibition ◽  
Tyrosinase Inhibitory Activity ◽  
Docking Simulations ◽  
Competitive Inhibitors ◽  
Human Tyrosinase

We previously reported (E)-β-phenyl-α,β-unsaturated carbonyl scaffold ((E)-PUSC) played an important role in showing high tyrosinase inhibitory activity and that derivatives with a 4-substituted resorcinol moiety as the β-phenyl group of the scaffold resulted in the greatest tyrosinase inhibitory activity. To examine whether the 4-substituted resorcinol moiety could impart tyrosinase inhibitory activity in the absence of the α,β-unsaturated carbonyl moiety of the (E)-PUSC scaffold, 10 urolithin derivatives were synthesized. To obtain more candidate samples, the lactone ring in synthesized urolithins was reduced to produce nine reduced urolithins. Compounds 1c (IC50 = 18.09 ± 0.25 μM), 1h (IC50 = 4.14 ± 0.10 μM), and 2a (IC50 = 15.69 ± 0.40 μM) had greater mushroom tyrosinase-inhibitory activities than kojic acid (KA) (IC50 = 48.62 ± 3.38 μM). The SAR results suggest that the 4-substituted resorcinol motif makes an important contribution to tyrosinase inhibition. To investigate whether these compounds bind to human tyrosinase, a human tyrosinase homology model was developed. Docking simulations with mushroom and human tyrosinases showed that 1c, 1h, and 2a bind to the active site of both tyrosinases with higher binding affinities than KA. Pharmacophore analyses showed that two hydroxyl groups of the 4-substituted resorcinol entity act as hydrogen bond donors in both mushroom and human tyrosinases. Kinetic analyses indicated that these compounds were all competitive inhibitors. Compound 2a inhibited cellular tyrosinase activity and melanogenesis in α-MSH plus IBMX-stimulated B16F10 melanoma cells more strongly than KA. These results suggest that 2a is a promising candidate for the treatment of skin pigment disorders, and show the 4-substituted resorcinol entity importantly contributes to tyrosinase inhibition.

scholarly journals The Effect of D-(−)-arabinose on Tyrosinase: An Integrated Study Using Computational Simulation and Inhibition Kinetics

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Hong-Jian Liu ◽  
Sunyoung Ji ◽  
Yong-Qiang Fan ◽  
Li Yan ◽  
Jun-Mo Yang ◽  
...  
Keyword(s):  
Active Site ◽  
Mixed Type ◽  
Computational Simulation ◽  
Dynamics Simulation ◽  
Hydroxyl Groups ◽  
Inhibition Kinetics ◽  
Tyrosinase Inhibition ◽  
Tyrosinase Inhibitors ◽  
Integrated Study ◽  
Mixed Type Inhibitor

Tyrosinase is a ubiquitous enzyme with diverse physiologic roles related to pigment production. Tyrosinase inhibition has been well studied for cosmetic, medicinal, and agricultural purposes. We simulated the docking of tyrosinase and D-(−)-arabinose and found a binding energy of −4.5 kcal/mol for theup-formof D-(−)-arabinose and −4.4 kcal/mol for thedown-form of D-(−)-arabinose. The results of molecular dynamics simulation suggested that D-(−)-arabinose interacts mostly with HIS85, HIS259, and HIS263, which are believed to be in the active site. Our kinetic study showed that D-(−)-arabinose is a reversible, mixed-type inhibitor of tyrosinase (α-value =6.11±0.98, Ki=0.21±0.19 M). Measurements of intrinsic fluorescence showed that D-(−)-arabinose induced obvious tertiary changes to tyrosinase (binding constant K=1.58±0.02 M−1, binding number n=1.49±0.06). This strategy of predicting tyrosinase inhibition based on specific interactions of aldehyde and hydroxyl groups with the enzyme may prove useful for screening potential tyrosinase inhibitors.

scholarly journals Molecular Dynamics Scoring of Protein–Peptide Models Derived from Coarse-Grained Docking

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3293
Author(s):  
Mateusz Zalewski ◽  
Sebastian Kmiecik ◽  
Michał Koliński
Keyword(s):  
Molecular Dynamics ◽  
Geometry Optimization ◽  
Computational Prediction ◽  
Md Simulations ◽  
Coarse Grained ◽  
Ligand Interaction ◽  
Vast Number ◽  
Docking Simulations ◽  
Peptide Models ◽  
Peptide Complexes

One of the major challenges in the computational prediction of protein–peptide complexes is the scoring of predicted models. Usually, it is very difficult to find the most accurate solutions out of the vast number of sometimes very different and potentially plausible predictions. In this work, we tested the protocol for Molecular Dynamics (MD)-based scoring of protein–peptide complex models obtained from coarse-grained (CG) docking simulations. In the first step of the scoring procedure, all models generated by CABS-dock were reconstructed starting from their original C-alpha trace representations to all-atom (AA) structures. The second step included geometry optimization of the reconstructed complexes followed by model scoring based on receptor–ligand interaction energy estimated from short MD simulations in explicit water. We used two well-known AA MD force fields, CHARMM and AMBER, and a CG MARTINI force field. Scoring results for 66 different protein–peptide complexes show that the proposed MD-based scoring approach can be used to identify protein–peptide models of high accuracy. The results also indicate that the scoring accuracy may be significantly affected by the quality of the reconstructed protein receptor structures.

scholarly journals Binding of Androgen- and Estrogen-Like Flavonoids to Their Cognate (Non)Nuclear Receptors: A Comparison by Computational Prediction

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1613
Author(s):  
Giulia D’Arrigo ◽  
Eleonora Gianquinto ◽  
Giulia Rossetti ◽  
Gabriele Cruciani ◽  
Stefano Lorenzetti ◽  
...  
Keyword(s):  
Nuclear Receptors ◽  
Fruits And Vegetables ◽  
Computational Prediction ◽  
Membrane Receptors ◽  
Computational Docking ◽  
Docking Simulations ◽  
Mediated Effects ◽  
17Β Estradiol ◽  
G Protein Coupled ◽  
Relevant Degree

Flavonoids are plant bioactives that are recognized as hormone-like polyphenols because of their similarity to the endogenous sex steroids 17β-estradiol and testosterone, and to their estrogen- and androgen-like activity. Most efforts to verify flavonoid binding to nuclear receptors (NRs) and explain their action have been focused on ERα, while less attention has been paid to other nuclear and non-nuclear membrane androgen and estrogen receptors. Here, we investigate six flavonoids (apigenin, genistein, luteolin, naringenin, quercetin, and resveratrol) that are widely present in fruits and vegetables, and often used as replacement therapy in menopause. We performed comparative computational docking simulations to predict their capability of binding nuclear receptors ERα, ERβ, ERRβ, ERRγ, androgen receptor (AR), and its variant ART877A and membrane receptors for androgens, i.e., ZIP9, GPRC6A, OXER1, TRPM8, and estrogens, i.e., G Protein-Coupled Estrogen Receptor (GPER). In agreement with data reported in literature, our results suggest that these flavonoids show a relevant degree of complementarity with both estrogen and androgen NR binding sites, likely triggering genomic-mediated effects. It is noteworthy that reliable protein–ligand complexes and estimated interaction energies were also obtained for some suggested estrogen and androgen membrane receptors, indicating that flavonoids could also exert non-genomic actions. Further investigations are needed to clarify flavonoid multiple genomic and non-genomic effects. Caution in their administration could be necessary, until the safe assumption of these natural molecules that are largely present in food is assured.

scholarly journals Analysis of binding energies between luciferin and luciferase adsorbed on Si surface by docking simulations

2007 ◽  
Vol 439 (1-3) ◽  
pp. 148-150
Author(s):  
Katsuhiko Nishiyama ◽  
Takanobu Watanabe ◽  
Tadatsugu Hoshino ◽  
Iwao Ohdomari
Keyword(s):  
Binding Energies ◽  
Docking Simulations

scholarly journals Bioinformatics Tools and Benchmarks for Computational Docking and 3D Structure Prediction of RNA-Protein Complexes

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 432 ◽  
Author(s):  
Chandran Nithin ◽  
Pritha Ghosh ◽  
Janusz Bujnicki
Keyword(s):  
Rna Splicing ◽  
Structure Prediction ◽  
Protein Complexes ◽  
3D Structure ◽  
Structural Models ◽  
Computational Prediction ◽  
Computational Docking ◽  
3D Structure Prediction ◽  
Rna Protein Complexes

RNA-protein (RNP) interactions play essential roles in many biological processes, such as regulation of co-transcriptional and post-transcriptional gene expression, RNA splicing, transport, storage and stabilization, as well as protein synthesis. An increasing number of RNP structures would aid in a better understanding of these processes. However, due to the technical difficulties associated with experimental determination of macromolecular structures by high-resolution methods, studies on RNP recognition and complex formation present significant challenges. As an alternative, computational prediction of RNP interactions can be carried out. Structural models obtained by theoretical predictive methods are, in general, less reliable compared to models based on experimental measurements but they can be sufficiently accurate to be used as a basis for to formulating functional hypotheses. In this article, we present an overview of computational methods for 3D structure prediction of RNP complexes. We discuss currently available methods for macromolecular docking and for scoring 3D structural models of RNP complexes in particular. Additionally, we also review benchmarks that have been developed to assess the accuracy of these methods.

scholarly journals Elucidation of the Interaction between Flavan-3-ols and Bovine Serum Albumin and Its Effect on Their In-Vitro Cytotoxicity

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3667
Author(s):  
Yasuyuki Fujii ◽  
Yoshitomo Suhara ◽  
Yusuke Sukikara ◽  
Tomohiro Teshima ◽  
Yoshihisa Hirota ◽  
...  
Keyword(s):  
Cell Culture ◽  
Bovine Serum Albumin ◽  
Serum Albumin ◽  
Bovine Serum ◽  
Fetal Bovine Serum ◽  
In Vitro Cytotoxicity ◽  
Binding Energies ◽  
Docking Simulations ◽  
Fetal Bovine

Flavan-3-ols (FLs), specifically catechin and its oligomer B-type procyanidins, are suggested to potently bind to bovine serum albumin (BSA). We examined the interaction between BSA and FLs by fluorescence quenching and found the following order of binding activities to BSA: cinnamtannin A2 (A2; tetramer) > procyanidin C1 (C1; trimer) ≈ procyanidin B2 (B2, dimer) > (−)epicatechin (EC, monomer). Docking simulations between BSA and each compound at the binding site showed that the calculated binding energies were consistent with the results of our experimental assay. FLs exerted cytotoxicity at 1000 μg/mL in F11 cell culture with fetal bovine serum containing BSA. In culture containing serum-free medium, FLs exhibited significant cell proliferation at 10−4 μg/mL and cytotoxicity was observed at concentrations greater than 10 μg/mL. Results of this study suggest that interactions between polyphenols and BSA should be taken into account when evaluating procyanidin in an in vitro cell culture system.

scholarly journals Dermatopontin in Skeletal Muscle Extracellular Matrix Regulates Myogenesis

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 332 ◽  
Author(s):  
Kim ◽  
Ahmad ◽  
Shaikh ◽  
Jan ◽  
Seo ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
In Silico ◽  
State Of The Art ◽  
Myogenic Differentiation ◽  
3D Structure ◽  
Inhibitory Effect ◽  
C2c12 Cells ◽  
Myoblast Differentiation ◽  
Protein Protein Interaction

Dermatopontin (DPT) is an extensively distributed non-collagenous component of the extracellular matrix predominantly found in the dermis of the skin, and consequently expressed in several tissues. In this study, we explored the role of DPT in myogenesis and perceived that it enhances the cell adhesion, reduces the cell proliferation and promotes the myoblast differentiation in C2C12 cells. Our results reveal an inhibitory effect with fibronectin (FN) in myoblast differentiation. We also observed that DPT and fibromodulin (FMOD) regulate positively to each other and promote myogenic differentiation. We further predicted the 3D structure of DPT, which is as yet unknown, and validated it using state-of-the-art in silico tools. Furthermore, we explored the in-silico protein-protein interaction between DPT-FMOD, DPT-FN, and FMOD-FN, and perceived that the interaction between FMOD-FN is more robust than DPT-FMOD and DPT-FN. Taken together, our findings have determined the role of DPT at different stages of the myogenic process.

Identification of chemical constituents from the bark of Larix kaempferi and their tyrosinase inhibitory effect

Holzforschung ◽  
2019 ◽  
Vol 73 (7) ◽  
pp. 637-643 ◽  
Author(s):  
Yuya Kakumu ◽  
Kosei Yamauchi ◽  
Tohru Mitsunaga
Keyword(s):  
Chemical Constituents ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Hydroxyl Group ◽  
Larix Kaempferi ◽  
Tyrosinase Inhibition ◽  
Ionization Time ◽  
Flight Mass Spectrometry ◽  
Potent Inhibition ◽  
Forestry Production

Abstract Most of the wood bark produced by the forestry production is discarded in spite of containing many kinds of the phytochemical ingredients. The aim of the present study was to identify secondary metabolites from the bark of Larix kaempferi generated as waste material and evaluate their potential as cosmetic agents. Eighteen compounds, including a novel phenanthrene, 4,6,7-trihydroxyphenanthrene-2-O-β-D-glucopyranoside (16), were isolated from the bark of L. kaempferi and identified by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) and nuclear magnetic resonance (NMR). In addition, the tyrosinase inhibitory activity of these compounds was evaluated. Procyanidin B7 (18) exhibited the most potent inhibition with IC50 values of 31.0 μM and 61.8 μM when using L-tyrosine and L-dopa as the substrate, respectively, which were similar to those of the positive control, kojic acid. Interestingly, quercetin-3-O-α-L-rhamnopyranoside (10) was shown to possess the tyrosinase inhibition although the other series of 3-glycoylated flavonols were not active, suggesting that the rhamnosyl group at C-3 and the hydroxyl group at C-3ʹ played an indispensable role in the anti-tyrosinase activity. These findings indicate that a number of constituents from L. kaempferi bark may have potential as additives in cosmetics.

scholarly journals Homology Modelling and Molecular Docking Studies of Selected Substituted Benzo[d]imidazol-1-yl)methyl)benzimidamide Scaffolds on Plasmodium falciparum Adenylosuccinate Lyase Receptor

2019 ◽  
Vol 13 ◽  
pp. 117793221986553 ◽  
Author(s):  
Gbolahan O Oduselu ◽  
Olayinka O Ajani ◽  
Yvonne U Ajamma ◽  
Benedikt Brors ◽  
Ezekiel Adebiyi
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
In Silico ◽  
Homology Modelling ◽  
3D Structure ◽  
Docking Studies ◽  
Binding Energies ◽  
Benzimidazole Derivatives ◽  
Adenylosuccinate Lyase ◽  
In Silico Admet

Plasmodium falciparum adenylosuccinate lyase ( PfADSL) is an important enzyme in purine metabolism. Although several benzimidazole derivatives have been commercially developed into drugs, the template design as inhibitor against PfADSL has not been fully explored. This study aims to model the 3-dimensional (3D) structure of PfADSL, design and predict in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) of 8 substituted benzo[ d]imidazol-1-yl)methyl)benzimidamide compounds as well as predict the potential interaction modes and binding affinities of the designed ligands with the modelled PfADSL. PfADSL 3D structure was modelled using SWISS-MODEL, whereas the compounds were designed using ChemDraw Professional. ADMET predictions were done using OSIRIS Property Explorer and Swiss ADME, whereas molecular docking was done with AutoDock Tools. All designed compounds exhibited good in silico ADMET properties, hence can be considered safe for drug development. Binding energies ranged from −6.85 to −8.75 kcal/mol. Thus, they could be further synthesised and developed into active commercial antimalarial drugs.

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