scholarly journals Screening of Human CYP1A2 and CYP3A4 Inhibitors from Seaweed In Silico and In Vitro

Marine Drugs ◽  
2020 ◽  
Vol 18 (12) ◽  
pp. 603
Author(s):  
Sung-Kun Yim ◽  
Kian Kim ◽  
SangHo Chun ◽  
TaeHawn Oh ◽  
WooHuk Jung ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
In Silico ◽  
Dependent Manner ◽  
Prosthetic Group ◽  
In Silico Modeling ◽  
Distal Surface ◽  
Ic50 Values ◽  
High Concentrations ◽  
Potential Inhibitors

Phenolic compounds and carotenoids are potential inhibitors of cytochrome P450s. Sixteen known compounds, phenolic compounds and carotenoids from seaweed were examined for potential inhibitory capacity against CYP1A2 and CYP3A4 in silico and in vitro. Morin, quercetin, and fucoxanthin inhibited the enzyme activity of CYP1A2 and CYP3A4 in a dose-dependent manner. The IC50 values of morin, quercetin, and fucoxanthin were 41.8, 22.5, and 30.3 μM for CYP1A2 and 86.6, 16.1, and 24.4 μM for CYP3A4, respectively. Siphonaxanthin and hesperidin did not show any significant effect on CYP1A2, but they slightly inhibited CYP3A4 activity at high concentrations. In silico modeling of CYP’s binding site revealed that the potential inhibitors bound in the cavity located above the distal surface of the heme prosthetic group through the 2a or 2f channel of CYPs. This study presents an approach for quickly predicting CYP inhibitory activity and shows the potential interactions of compounds and CYPs through in silico modeling.

scholarly journals SARS-CoV-2 Papain-Like Protease Potential Inhibitors—In Silico Quantitative Assessment

2021 ◽  
Vol 22 (8) ◽  
pp. 3957
Author(s):  
Adam Stasiulewicz ◽  
Alicja W. Maksymiuk ◽  
Mai Lan Nguyen ◽  
Barbara Bełza ◽  
Joanna I. Sulkowska
Keyword(s):  
In Silico ◽  
Multiple Linear Regression Model ◽  
Binding Mode ◽  
Host Proteins ◽  
Human Ubiquitin ◽  
Ic50 Values ◽  
Potential Activity ◽  
Carboxy Terminal ◽  
Potential Inhibitors

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes the papain-like protease (PLpro). The protein not only plays an essential role in viral replication but also cleaves ubiquitin and ubiquitin-like interferon-stimulated gene 15 protein (ISG15) from host proteins, making it an important target for developing new antiviral drugs. In this study, we searched for novel, noncovalent potential PLpro inhibitors by employing a multistep in silico screening of a 15 million compound library. The selectivity of the best-scored compounds was evaluated by checking their binding affinity to the human ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), which, as a deubiquitylating enzyme, exhibits structural and functional similarities to the PLpro. As a result, we identified 387 potential, selective PLpro inhibitors, from which we retrieved the 20 best compounds according to their IC50 values toward PLpro estimated by a multiple linear regression model. The selected candidates display potential activity against the protein with IC50 values in the nanomolar range from approximately 159 to 505 nM and mostly adopt a similar binding mode to the known, noncovalent SARS-CoV-2 PLpro inhibitors. We further propose the six most promising compounds for future in vitro evaluation. The results for the top potential PLpro inhibitors are deposited in the database prepared to facilitate research on anti-SARS-CoV-2 drugs.

Chickpea (Cicer arietinum L.) Lectin Exhibit Inhibition of ACE-I, α-amylase and α-glucosidase Activity

2019 ◽  
Vol 26 (7) ◽  
pp. 494-501 ◽  
Author(s):  
Sameer Suresh Bhagyawant ◽  
Dakshita Tanaji Narvekar ◽  
Neha Gupta ◽  
Amita Bhadkaria ◽  
Ajay Kumar Gautam ◽  
...  
Keyword(s):  
Biological Effects ◽  
Exchange Chromatography ◽  
Health Concern ◽  
Carbohydrate Binding ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ic50 Values ◽  
Chickpea Lectin

Background: Diabetes and hypertension are the major health concern and alleged to be of epidemic proportions. This has made it a numero uno subject at various levels of investigation. Glucosidase inhibitor provides the reasonable option in treatment of Diabetes Mellitus (DM) as it specifically targets post prandial hyperglycemia. The Angiotensin Converting Enzyme (ACE) plays an important role in hypertension. Therefore, inhibition of ACE in treatment of elevated blood pressure attracts special interest of the scientific community. Chickpea is a food legume and seeds contain carbohydrate binding protein- a lectin. Some of the biological properties of this lectin hitherto been elucidated. Methods: Purified by ion exchange chromatography, chickpea lectin was tested for its in vitro antioxidant, ACE-I inhibitory and anti-diabetic characteristic. Results: Lectin shows a characteristic improvement over the synthetic drugs like acarbose (oral anti-diabetic drug) and captopril (standard antihypertensive drug) when, their IC50 values are compared. Lectin significantly inhibited α-glucosidase and α-amylase in a concentration dependent manner with IC50 values of 85.41 ± 1.21 ҝg/ml and 65.05 ± 1.2 µg/ml compared to acarbose having IC50 70.20 ± 0.47 value of µg/ml and 50.52 ± 1.01 µg/ml respectively. β-Carotene bleaching assay showed antioxidant activity of lectin (72.3%) to be as active as Butylated Hydroxylanisole (BHA). In addition, lectin demonstrated inhibition against ACE-I with IC50 value of 57.43 ± 1.20 µg/ml compared to captopril. Conclusion: Lectin demonstrated its antioxidant character, ACE-I inhibition and significantly inhibitory for α-glucosidase and α-amylase seems to qualify as an anti-hyperglycemic therapeutic molecule. The biological effects of chickpea lectin display potential for reducing the parameters of medically debilitating conditions. These characteristics however needs to be established under in vivo systems too viz. animals through to humans.

In vitro and in silico modeling of endovascular stroke treatments for acute ischemic stroke

2021 ◽  
pp. 110693
Author(s):  
Giulia Luraghi ◽  
Rachel M. E. Cahalane ◽  
Emma van de Ven ◽  
Serena Overschie ◽  
Frank J. H. Gijsen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
In Silico ◽  
In Silico Modeling

scholarly journals Influence of the temperature factor on regeneration features of Silene Jailensis N.I. Rubtzov and Crepis Purpurea (Willd.) M. Bieb. and the content of phenolic substances in vitro

2020 ◽  
pp. 87-96
Author(s):  
I. V. Mitrofanova ◽  
N. N. Ivanova ◽  
A. E. Paliy ◽  
I. N. Paliy ◽  
O. V. Mitrofanova
Keyword(s):  
Phenolic Compounds ◽  
Biochemical Study ◽  
Adventitious Shoots ◽  
Maximum Growth ◽  
Rare Plant ◽  
Temperature Influence ◽  
Phenolic Substances ◽  
Morphogenetic Potential ◽  
High Concentrations

The results of temperature influence on the regeneration of microshoots and the level of phenolic compounds in microshoots of two rare plant species under in vitro conditions are presented. It is shown that the maximum growth of the main and the formation of adventitious shoots, leaves occurred at a temperature of 21- 23°C. Reconnaissance experiments on the biochemical study of organs and tissues of the studied species were conducted. It was found that the leaves contain high concentrations of phenolic substances and are characterized by a wide variety of components. It is shown that as the temperature increased, the content of the sum of phenolic substances increased, which negatively affected the morphogenetic potential of the studied species.

Bioactivities of Achillea phrygia and Bupleurum croceum based on the composition of phenolic compounds: In vitro and in silico approaches

2017 ◽  
Vol 107 ◽  
pp. 597-608 ◽  
Author(s):  
Gokhan Zengin ◽  
Gizem Bulut ◽  
Adriano Mollica ◽  
Mehmet Zeki Haznedaroglu ◽  
Ahmet Dogan ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
In Silico

Effects of polymethoxylated flavone metabolites on apoB100 secretion and MTP activity in Huh7.5 cells

2021 ◽  
Vol 18 ◽  
Author(s):  
Danielle R. Gonçalves ◽  
Thais B. Cesar ◽  
John A. Manthey ◽  
Paulo I. Costa
Keyword(s):  
Lipid Synthesis ◽  
Dependent Manner ◽  
Transfer Protein ◽  
Low Concentrations ◽  
Wide Range ◽  
Cell Assays ◽  
Polymethoxylated Flavones ◽  
High Concentrations

Background: Citrus polymethoxylated flavones (PMFs) reduce the synthesis of liver lipoproteins in animal and in vitro cell assays, but few studies have evaluated the direct effects of their metabolites on this highly regulated process. Objective: To investigate the effects of representative metabolites of PMF on the secretion of liver lipoproteins using the mammalian cell Huh7.5. Method: In this study, the influences of three PMFs and five previously isolated PMF metabolites on hepatic apoB-100 secretion and microsomal transfer protein (MTP) activity were evaluated. Tangeretin (TAN), nobiletin (NOB) and 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF), and their glucuronides (TAN-Gluc, NOB-Gluc and HMF-Gluc) and oxidatively demethylated metabolites (TAN-OH, NOB-OH, HMF-OH) were incubated with Huh7.5 cells to measure their inhibitory effects on lipid synthesis. Results: The results showed that TAN, HMF and TAN-OH reduced the secretion of apoB-100 in a dose-dependent manner, while NOB and the other tested metabolites showed no inhibition. MTP activity in the Huh7.5 cells was significantly reduced in the presence of low concentrations of TAN, and in high concentrations of NOB-OH. This study also showed that PMFs and PMF metabolites produced a wide range of effects on apoB-100 secretion and MTP activity. Conclusion: The results suggest that while PMFs and their metabolites control dyslipidemia in vivo, the inhibition of MTP activity cannot be the only pathway influenced by these compounds.

scholarly journals In Silico and In Vitro Anti-Helicobacter Pylori Effects of Combinations of Phytochemicals and Antibiotics

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3608 ◽  
Author(s):  
Pedro Fong ◽  
Chon-Hou Hao ◽  
Chi-Cheng Io ◽  
Pou-Io Sin ◽  
Li-Rong Meng
Keyword(s):  
Helicobacter Pylori ◽  
In Silico ◽  
Inhibitory Concentration ◽  
Positive Control ◽  
Shikimate Kinase ◽  
Semialdehyde Dehydrogenase ◽  
Class 1 ◽  
H Pylori ◽  
Potential Inhibitors

Helicobacter pylori infection is a WHO class 1 carcinogenic factor of gastric adenocarcinoma. In the past decades, many studies have demonstrated the increasing trend of antibiotic resistance and pointed out the necessity of new effective treatment. This study was aimed at identifying phytochemicals that can inhibit H. pylori and possibly serve as adjuvant treatments. Here, in silico molecular docking and drug-like properties analyses were performed to identify potential inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase. These three enzymes are targets of the treatment of H. pylori. Susceptibility and synergistic testing were performed on the selected phytochemicals and the positive control antibiotic, amoxicillin. The in-silico study revealed that oroxindin, rosmarinic acid and verbascoside are inhibitors of urease, shikimate kinase and aspartate-semialdehyde dehydrogenase, respectively, in which, oroxindin has the highest potency against H. pylori, indicated by a minimum inhibitory concentration (MIC) value of 50 μg/mL. A combination of oroxindin and amoxicillin demonstrated additive effects against H. pylori, as indicated by a fractional inhibitory concentration (FIC) value of 0.75. This study identified phytochemicals that deserve further investigation for the development of adjuvant therapeutic agents to current antibiotics against H. pylori.

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