scholarly journals Characterizing Tyrosinase Modulators from the Roots of Angelica keiskei Using Tyrosinase Inhibition Assay and UPLC-MS/MS as the Combinatorial Novel Approach

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3297 ◽  
Author(s):  
Jia-Hao Lee ◽  
Hui-Ching Mei ◽  
I-Chih Kuo ◽  
Tzong-Huei Lee ◽  
Yu-Hsin Chen ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Ultra Performance Liquid Chromatography ◽  
Rapid Screening ◽  
Inhibition Assay ◽  
Tyrosinase Inhibition ◽  
Novel Approach ◽  
Ic50 Values ◽  
Angelica Keiskei ◽  
Screening And Identification

In this study, an in vitro tyrosinase inhibition assay in combination with ultra performance liquid chromatography-orbitrap mass spectrometry (UPLC-orbitrap-MS) was developed for the rapid screening and identification of tyrosinase modulators from roots of Angelica keiskei. Of the 15 candidates considered, nine chalcones, xanthoangelols (1), B (2), D (3), E (4), G (5), H (6), 4-hydroxyderricin (7), xanthokeismin B (8) and (2E)-1-[4-hydroxy-2-(2-hydroxy-2-propanyl)-2,3-dihydro-1-benzofuran-7-yl]-3-(4-hydroxyphenyl)-2-propen-1-one (9), five coumarins, umbelliferone (10), selinidin (11), isopimpinellin (12), phellopterin (13) and xanthyletin (14), and one other compound, ashitabaol A (15), were distinguished between the test samples and the controls with statistical significance, and the structure of each compound was determined by comparing with in-house standards and the literature. Among these, six compounds, xanthoangelol (1), xanthoangelol D (3), xanthoangelol H (6), 4-hydroxyderricin (7), laserpitin (16) and isolaserpitin (17), were isolated from roots of A. keiskei. Of the compounds isolated, compounds 1, 7 and 16 were subjected to tyrosinase inhibitory assay, and the IC50 values were 15.87 ± 1.21, 60.14 ± 2.29 and >100 μM, respectively. The present study indicated that the combination of in vitro tyrosinase inhibition assay coupled with UPLC-MS/MS could be widely applied to the rapid screening of active substances from various natural resources.

scholarly journals Momilactones A, B, and Tricin in Rice Grain and By-Products are Potential Skin Aging Inhibitors

Foods ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 602 ◽  
Author(s):  
Nguyen Van Quan ◽  
Dam Duy Thien ◽  
Tran Dang Khanh ◽  
Hoang-Dung Tran ◽  
Tran Dang Xuan
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Biological Activities ◽  
Ultra Performance Liquid Chromatography ◽  
Skin Aging ◽  
Ionization Mass ◽  
Rice Grain ◽  
Synergistic Activity ◽  
Ic50 Values

We previously reported the inhibitory potentials of momilactones A (MA) and B (MB) against key enzymes related to type 2 diabetes and obesity. In this study, antioxidant and anti-skin-aging activities of MA and MB were investigated and compared with tricin, a well-known antioxidant and antiaging flavonoid in rice. MA, MB, and tricin were purified from rice husk by column chromatography and their biological activities were subsequently assayed by in vitro trials. The contents of MA, MB, and tricin of different commercial rice cultivars in Japan were quantified and confirmed by ultra-performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS) and high-performance liquid chromatography (HPLC) analyses. The antioxidant assays revealed a synergistic activity of the mixture MA and MB (MAB, 1:1, v/v). In addition, in 2,2’-azino-bis (ABTS) assay, IC50 values of MAB (0.3 mg/mL) and tricin (0.3 mg/mL) was 4-fold and 9-fold greater than that of individual MB (1.3 mg/mL) or MA (2.8 mg/mL), respectively. The in vitro enzymatic assays on pancreatic elastase and tyrosinase indicated that MA and MB were potential to relief skin wrinkles and freckles. In detail, MA exerted higher inhibition on both enzymatic activities (30.9 and 37.6% for elastase and tyrosinase inhibition, respectively) than MB (18.5 and 12.6%) and MAB (32.0 and 19.7%) at a concentration of 2.0 mg/mL. Notably, MA and the mixture MAB exhibited stronger inhibitions on elastase and tyrosinase in comparison with tricin and vanillin. MA, MB, and tricin in rice are potential to develop cosmetics as well as supplements for skin aging treatments.

scholarly journals Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7095
Author(s):  
Galyna Volynets ◽  
Hanna Vyshniakova ◽  
Georgiana Nitulescu ◽  
George Mihai Nitulescu ◽  
Anca Ungurianu ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Multidrug Resistant ◽  
Molecular Target ◽  
Biological Research ◽  
Sortase A ◽  
Phenotypic Screening ◽  
Inhibition Assay ◽  
Activity Inhibition ◽  
Ic50 Values

Staphylococcus aureus (S. aureus) is a causative agent of many hospital- and community-acquired infections with the tendency to develop resistance to all known antibiotics. Therefore, the development of novel antistaphylococcal agents is of urgent need. Sortase A is considered a promising molecular target for the development of antistaphylococcal agents. The main aim of this study was to identify novel sortase A inhibitors. In order to find novel antistaphylococcal agents, we performed phenotypic screening of a library containing 15512 compounds against S. aureus ATCC43300. The molecular docking of hits was performed using the DOCK program and 10 compounds were selected for in vitro enzymatic activity inhibition assay. Two inhibitors were identified, N,N-diethyl-N′-(5-nitro-2-(quinazolin-2-yl)phenyl)propane-1,3-diamine (1) and acridin-9-yl-(1H-benzoimidazol-5-yl)-amine (2), which decrease sortase A activity with IC50 values of 160.3 µM and 207.01 µM, respectively. It was found that compounds 1 and 2 possess antibacterial activity toward 29 tested multidrug resistant S. aureus strains with MIC values ranging from 78.12 to 312.5 mg/L. These compounds can be used for further structural optimization and biological research.

scholarly journals Ligand-Based and Docking-Based Virtual Screening of MDM2 Inhibitors as Potent Anticancer Agents

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Bing-Hui Li ◽  
Jun-Qi Ge ◽  
Ya-Li Wang ◽  
Li-Jun Wang ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Antiproliferative Activity ◽  
Pharmacophore Model ◽  
Inhibition Assay ◽  
Ic50 Values

A ligand-based and docking-based virtual screening was carried out to identify novel MDM2 inhibitors. A pharmacophore model with four features was used for virtual screening, followed by molecular docking. Seventeen compounds were selected for an in vitro MDM2 inhibition assay, and compounds AO-476/43250177, AG-690/37072075, AK-968/15254441, AO-022/43452814, and AF-399/25108021 showed promising MDM2 inhibition activities with K i values of 9.5, 8.5, 23.4, 3.2, and 23.1 μM, respectively. Four compounds also showed antiproliferative activity, and compound AO-022/43452814 was the most potent hit with IC50 values of 19.35, 26.73, 12.63, and 24.14 μM against MCF7 (p53 +/+), MCF7 (p53 -/-), HCT116 (p53 +/+), and HCT116 (p53 -/-) cell lines, respectively. Compound AO-022/43452814 could be used as a scaffold for the development of anticancer agents targeting MDM2.

COMPARATIVE IN VITRO ANTIDIABETIC ACTIVITY OF PRUNUS AMYGDALUS (BAIL.) AND HIBISCUS ROSA-SINENSIS (LINN.)

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (04) ◽  
pp. 29-31
Author(s):  
Keyword(s):  
Aqueous Extract ◽  
Ethanolic Extract ◽  
Antidiabetic Activity ◽  
Assay Method ◽  
Inhibition Assay ◽  
Phytochemical Screening ◽  
Prunus Amygdalus ◽  
Hibiscus Rosa Sinensis ◽  
Ic50 Values

A comparative study was designed to evaluate the in vitro antidiabetic activity from the aqueous extract of dried pericarp of Prunus amygdalus Bail and ethanolic extract of dried flower of Hibiscus rosa-sinensis L. against the standard Acarbose.The aqueous extract of P. amygdalus and ethanolic extract of H. rosa-sinensis were extracted by the continuous hot extraction process.The qualitative phytochemical screening of aqueous extract and ethanolic extract reveals the presence of phytosterols, phenols, carbohydrates, flavanoids, saponins, amino acids and alkaloids, phenol, tannins, cardiac glycoside, saponin and flavonoids, respectively. In vitro pharmacological activity of P. amygdalus and H.rosa-sinensis were performed and compared by α-amylase inhibition assay method. The percentage inhibition of α-amylase by P. amygdalus, H. rosa-sinensis and Acarbose (50 &100 μg/mL) at dose of 50mg/mL and 100mg/mL were found to be 60.11±2.74%,74.86±0.31*%, 71.36± 1.86%, 81.49±1.72%, 82.33±1.10% and 95.37±0.56*%, respectively. The IC50 values were found to be 40.26μg/mL for acarbose, 49.63mg/mL for ethanolic extract of H. rosa-sinensis and 56.42mg/mL for aqueous extract of P. amygdalus.

scholarly journals DESIGN, SYNTHESIS AND COX1/2 INHIBITORY ACTIVITY OF NEW QUINAZOLINE-5-ONE DERIVATIVES

2017 ◽  
Vol 13 (1) ◽  
pp. 5923-5931
Author(s):  
Ahmed S. Aboraia ◽  
Mohammed A. Hara ◽  
Mostafa H. Abdelrahman ◽  
Mohamed M. Amin ◽  
Osama I. El-Sabbaghab
Keyword(s):  
Active Site ◽  
Docking Study ◽  
Selectivity Index ◽  
Inhibition Assay ◽  
Inhibitor Concentration ◽  
Design Synthesis ◽  
Ic50 Values ◽  
Cox 2 ◽  
Cox 1

A new series of 1-(4-Acetylphenyl)-7,7-dimethyl-3-(substitutedphenyl)-1,2,3,4,7,8-octahydroquinazolin-5(6H)-ones (6-15) were synthesized and tested against COX-1 and COX-2 enzymes. Those compounds exhibited strong interaction at the COX-2 binding site and poor interaction at the COX-1 active site. Subjected to in vitro cyclooxygenase COX-1/COX-2 inhibition assay; most of the compounds especially compounds 6, 7, 12, 13, and 16 exhibited potent anti-inflammatory effects, selective COX-2 inhibition, with half-maximal inhibitor concentration (IC50) values of 0.22–1.42 μM and selectivity index (SI) values of 6.16–14.18 compared with celecoxib (IC50 = 0.05 μM and COX-2 SI: 296), diclofenac (IC50 = 0.8 μM and COX-2 SI: 4.87), and indomethacin (IC50 = 0.49 μM and COX-2 SI: 0.08) as reference drugs. Docking study has been carried out to confirm the binding affinity and selectivity of the most active compound (compound 6) to COX-2 enzyme.

scholarly journals SARS CoV-2 Nucleocapsid Protein-mediated Enhancement of Spike pseudotyped Lentivirus Infectivity and Loss of Sensitivity to Neutralisation

2021 ◽  
Author(s):  
Tarun Mishra ◽  
M Sreepadmanabh ◽  
Ajit Chande
Keyword(s):  
Neutralizing Antibodies ◽  
Lentiviral Vector ◽  
Virus Production ◽  
Rapid Screening ◽  
Vector System ◽  
N Gene ◽  
N Protein ◽  
Entry Inhibitors ◽  
Screening And Identification

BACKGROUND: The causative agent of the ongoing COVID-19 pandemic, SARS CoV-2, is a highly pathogenic virus requiring specialized biocontainment facilities. However, pseudotyping-based approaches using the spike glycoprotein have allowed for their study in BSL-2 level laboratories, enabling the rapid screening and identification of neutralizing antibodies, entry inhibitors, host factors, and therapeutic agents. However, this minimalist approach fails to capture the possible contributions and roles of other SARS CoV-2 genes in the entry process. OBJECTIVES: To determine the relative effects of structural and non-structural genes of the SARS CoV-2 on the infectivity of spike-pseudotyped particles, using a lentiviral vector system. METHODS AND RESULTS: An unbiased co-transfection screen of twenty-four SARS CoV-2 genes revealed the nucleocapsid (N) protein as a prime promoter of spike-pseudotyped lentivirus infectivity, as assayed by transduction of an ACE2+ cell line. The spike protein was also observed to be enriched in virions when augmented by the presence of the N gene during virus production. Further, N-enhanced spike-pseudoviruses exhibited a lowered sensitivity to neutralisation by an IgG-Fc fused ACE2 microbody. These results highlight the broad importance of incorporating specific accessory genes during spike-pseudovirus preparation, which may help better recapitulate a physiologically relevant in vitromodel for SARS CoV-2 infectivity.

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