scholarly journals Estimation of Inhibitory Effect against Tyrosinase Activity through Homology Modeling and Molecular Docking

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Daungkamon Nokinsee ◽  
Lalida Shank ◽  
Vannajan Sanghiran Lee ◽  
Piyarat Nimmanpipug
Keyword(s):  
Md Simulation ◽  
Inhibitory Effect ◽  
Human Model ◽  
Mushroom Tyrosinase ◽  
Whitening Agent ◽  
Human Enzyme ◽  
Cosmetic Industry ◽  
Key Enzyme ◽  
Docking Calculations ◽  
Automated Docking

Tyrosinase is a key enzyme in melanogenesis. Generally, mushroom tyrosinase from A. bisporus had been used as a model in skin-whitening agent tests employed in the cosmetic industry. The recently obtained crystal structure of bacterial tyrosinase from B. megaterium has high similarity (33.5%) to the human enzyme and thus it was used as a template for constructing of the human model. Binding of tyrosinase to a series of its inhibitors was simulated by automated docking calculations. Docking and MD simulation results suggested that N81, N260, H263, and M280 are involved in the binding of inhibitors to mushroom tyrosinase. E195 and H208 are important residues in bacterial tyrosinase, while E230, S245, N249, H252, V262, and S265 bind to inhibitors and are important in forming pi interaction in human tyrosinase.

scholarly journals Tyrosinase-Targeting Gallacetophenone Inhibits Melanogenesis in Melanocytes and Human Skin- Equivalents

2020 ◽  
Vol 21 (9) ◽  
pp. 3144 ◽  
Author(s):  
Ji Young Lee ◽  
Jooyun Lee ◽  
Daejin Min ◽  
Juewon Kim ◽  
Hyoung-June Kim ◽  
...  
Keyword(s):  
Human Skin ◽  
Hydrophobic Interactions ◽  
Copper Ions ◽  
Inhibitory Effect ◽  
Compound Library ◽  
Tyrosinase Inhibition ◽  
Skin Model ◽  
Cosmetic Industry ◽  
Key Enzyme ◽  
Computational Molecular Modeling

Demands for safe depigmentation compounds are constantly increasing in the pharmaceutical and cosmetic industry, since the numerous relevant compounds reported to date have shown undesirable side effects or low anti-melanogenic effects. In this study, we reported three novel inhibitors of tyrosinase, which is the key enzyme in melanogenesis, identified using docking-based high throughput virtual screening of an in-house natural compound library followed by mushroom tyrosinase inhibition assay. Of the three compounds, gallacetophenone showed high anti-melanogenic effect in both human epidermal melanocytes and a 3D human skin model, MelanoDerm. The inhibitory effect of gallacetophenone on tyrosinase was elucidated by computational molecular modeling at the atomic level. Binding of gallacetophenone to the active site of tyrosinase was found to be stabilized by hydrophobic interactions with His367, Ile368, and Val377; hydrogen bonding with Ser380 and a water molecule bridging the copper ions. Thus, our results strongly suggested gallacetophenone as an anti-melanogenic ingredient that inhibits tyrosinase.

scholarly journals Identification and Characterization of NTB451 as a Potential Inhibitor of Necroptosis

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2884 ◽  
Author(s):  
Eun-Jung In ◽  
Yuno Lee ◽  
Sushruta Koppula ◽  
Tae-Yeon Kim ◽  
Jun-Hyuk Han ◽  
...  
Keyword(s):  
Cell Death ◽  
Md Simulation ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Direct Interaction ◽  
Inhibitory Effect ◽  
Therapeutic Implications ◽  
Pathological Conditions ◽  
Tnf Α

Necroptosis, or caspase-independent programmed cell death, is known to be involved in various pathological conditions, such as ischemia/reperfusion injury, myocardial infarction, atherosclerosis, and inflammatory bowel diseases. Although several inhibitors of necroptosis have been identified, none of them are currently in clinical use. In the present study, we identified a new compound, 4-({[5-(4-aminophenyl)-4-ethyl-4H-1,2,4-triazol-3-yl]sulfanyl}methyl)-N-(1,3-thiazol-2-yl) benzamide (NTB451), with significant inhibitory activity on the necroptosis induced by various triggers, such as tumor necrosis factor-α (TNF-α) and toll-like receptor (TLR) agonists. Mechanistic studies revealed that NTB451 inhibited phosphorylation and oligomerization of mixed lineage kinase domain like (MLKL), and this activity was linked to its inhibitory effect on the formation of the receptor interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3 complex. Small interfering RNA (siRNA)-mediated RIPK1 knockdown, drug affinity responsive target stability assay, and molecular dynamics (MD) simulation study illustrated that RIPK1 is a specific target of NTB451. Moreover, MD simulation showed a direct interaction of NTB451 and RIPK1. Further experiments to ensure that the inhibitory effect of NTB451 was restricted to necroptosis and NTB451 had no effect on nuclear factor-κB (NF-κB) activation or apoptotic cell death upon triggering with TNF-α were also performed. Considering the data obtained, our study confirmed the potential of NTB451 as a new necroptosis inhibitor, suggesting its therapeutic implications for pathological conditions induced by necroptotic cell death.

scholarly journals cDNA cloning of human and rat brain myo-inositol monophosphatase. Expression and characterization of the human recombinant enzyme

1992 ◽  
Vol 284 (3) ◽  
pp. 749-754 ◽  
Author(s):  
G McAllister ◽  
P Whiting ◽  
E A Hammond ◽  
M R Knowles ◽  
J R Atack ◽  
...  
Keyword(s):  
Rat Brain ◽  
Cell Signalling ◽  
Biochemical Properties ◽  
Recombinant Enzyme ◽  
Cdna Clones ◽  
Coding Region ◽  
Inositol Monophosphatase ◽  
Human Enzyme ◽  
Key Enzyme

Inositol monophosphatase (EC 3.1.3.25) is a key enzyme in the phosphoinositide cell-signalling system. Its role is to provide inositol required for the resynthesis of phosphatidylinositol and polyphosphoinositides. It is the probable pharmacological target for lithium action in brain. Using probes derived from the bovine inositol monophosphatase cDNA we have isolated cDNA clones encoding the human and rat brain enzymes. The enzyme is highly conserved in all three species (79% identical). The coding region of the human cDNA was inserted into a bacterial expression vector. The expressed recombinant enzyme was purified and its biochemical properties examined. The human enzyme is very similar to the bovine enzyme.

scholarly journals Psoromic Acid, a Lichen-Derived Molecule, Inhibits the Replication of HSV-1 and HSV-2, and Inactivates HSV-1 DNA Polymerase: Shedding Light on Antiherpetic Properties

Molecules ◽  
2019 ◽  
Vol 24 (16) ◽  
pp. 2912 ◽  
Author(s):  
Sherif T. S. Hassan ◽  
Miroslava Šudomová ◽  
Kateřina Berchová-Bímová ◽  
Karel Šmejkal ◽  
Javier Echeverría
Keyword(s):  
Dna Polymerase ◽  
Active Sites ◽  
Inhibitory Action ◽  
Inhibitory Concentration ◽  
Competitive Inhibition ◽  
Inhibitory Effect ◽  
Standard Drug ◽  
Key Enzyme ◽  
Hsv 1

Psoromic acid (PA), a bioactive lichen-derived compound, was investigated for its inhibitory properties against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), along with the inhibitory effect on HSV-1 DNA polymerase, which is a key enzyme that plays an essential role in HSV-1 replication cycle. PA was found to notably inhibit HSV-1 replication (50% inhibitory concentration (IC50): 1.9 μM; selectivity index (SI): 163.2) compared with the standard drug acyclovir (ACV) (IC50: 2.6 μM; SI: 119.2). The combination of PA with ACV has led to potent inhibitory activity against HSV-1 replication (IC50: 1.1 µM; SI: 281.8) compared with that of ACV. Moreover, PA displayed equivalent inhibitory action against HSV-2 replication (50% effective concentration (EC50): 2.7 μM; SI: 114.8) compared with that of ACV (EC50: 2.8 μM; SI: 110.7). The inhibition potency of PA in combination with ACV against HSV-2 replication was also detected (EC50: 1.8 µM; SI: 172.2). Further, PA was observed to effectively inhibit HSV-1 DNA polymerase (as a non-nucleoside inhibitor) with respect to dTTP incorporation in a competitive inhibition mode (half maximal inhibitory concentration (IC50): 0.7 μM; inhibition constant (Ki): 0.3 μM) compared with reference drugs aphidicolin (IC50: 0.8 μM; Ki: 0.4 μM) and ACV triphosphate (ACV-TP) (IC50: 0.9 μM; Ki: 0.5 μM). It is noteworthy that the mechanism by which PA-induced anti-HSV-1 activity was related to its inhibitory action against HSV-1 DNA polymerase. Furthermore, the outcomes of in vitro experiments were authenticated using molecular docking analyses, as the molecular interactions of PA with the active sites of HSV-1 DNA polymerase and HSV-2 protease (an essential enzyme required for HSV-2 replication) were revealed. Since this is a first report on the above-mentioned properties, we can conclude that PA might be a future drug for the treatment of HSV infections as well as a promising lead molecule for further anti-HSV drug design.

PP-34 Luteolin as a whitening agent with IL-1alpha, IL-6 and melanogenesis inhibitory effect from zostera marina L.

2003 ◽  
Vol 16 (5) ◽  
pp. 604-604
Author(s):  
Kyung Eun Lee ◽  
Sung Min Park ◽  
Jin Hui Kim ◽  
Bum Chun Lee ◽  
Hyeong Bae Pyo
Keyword(s):  
Zostera Marina ◽  
Inhibitory Effect ◽  
Whitening Agent

scholarly journals Antifungal and antioxidant activities of mature leaves of Myrcia splendens (Sw.) DC.

2019 ◽  
Vol 79 (1) ◽  
pp. 127-132
Author(s):  
F. C. Pontes ◽  
V. C. P. Abdalla ◽  
M. Imatomi ◽  
L. F. G. Fuentes ◽  
S. C. J. Gualtieri
Keyword(s):  
Antioxidant Activity ◽  
Mycelial Growth ◽  
Antioxidant Activities ◽  
Pathogenic Fungus ◽  
Radical Scavenging ◽  
Inhibitory Effect ◽  
Antioxidant Potential ◽  
Economic Losses ◽  
Mature Leaves ◽  
Cosmetic Industry

Abstract In recent years, natural products with antifungal and antioxidant activities are being increasingly researched for a more sustainable alternative to the chemicals currently used for the same purpose. The plant pathogenic fungus Alternaria alternata is a causative agent of diseases in citrus, leading to huge economic losses. Antioxidants are important for the production of medicines for various diseases that may be related to the presence of free radicals, such as cancer, and in the cosmetic industry as an anti-aging agent and the food industry as preservatives. This study evaluated the antifungal and antioxidant potential of extracts of mature leaves of Myrcia splendens, a tree species that occurs in the Brazilian Cerrado. The antioxidant potential was analyzed by an assay of 1,1-diphenyl-2-picrylhydrazyl radical-scavenging method, and the antifungal activity was assessed through the evaluation of mycelial growth. Majority of the extracts exhibited a strong antioxidant activity, especially the acetonic extract (4A). The antioxidant activity may be related to the presence of phenolic compounds. However, the extracts showed no inhibitory activity of mycelial growth of the fungus tested, with the exception of dichloromethanic extract (2B), which had an inhibitory effect (10.2%) at the end of testing.

scholarly journals Modulation of inherent dynamical tendencies of the bisabolyl cation via preorganization in epi-isozizaene synthase

2015 ◽  
Vol 6 (4) ◽  
pp. 2347-2353 ◽  
Author(s):  
Ryan P. Pemberton ◽  
Krystina C. Ho ◽  
Dean J. Tantillo
Keyword(s):  
Quantum Chemical ◽  
Product Distribution ◽  
Terpene Synthase ◽  
Chemical Dynamics ◽  
Relative Importance ◽  
Docking Calculations ◽  
Automated Docking

The relative importance of various factors controlling the product distribution for a terpene synthase are elucidated through a combination of quantum chemical, dynamics and automated docking calculations.

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