scholarly journals Isolation of Novel ACE-Inhibitory and Antioxidant Peptides from Quinoa Bran Albumin Assisted with an In Silico Approach: Characterization, In Vivo Antihypertension, and Molecular Docking

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4562 ◽  
Author(s):  
Yajun Zheng ◽  
Xian Wang ◽  
Yongliang Zhuang ◽  
Yan Li ◽  
Hailong Tian ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Molecular Docking ◽  
In Silico ◽  
Bioactive Peptides ◽  
Docking Simulation ◽  
Reversed Phase ◽  
Scavenging Activity ◽  
Antioxidant Peptides ◽  
Ace Inhibitory

Albumin is the major fraction of quinoa protein that is characterized as having high nutritional value. However, until now, scant information is available on the bioactivity of quinoa albumin or its hydrolysates. To promote its usage, we extracted albumin in this study from quinoa bran assisted with cellulase and hemicellulose, and hydrolyzed it by alcalase and trypsin to produce bioactive peptides. The hydrolysates (QBAH) were purified by gel filtration and reversed-phase high-performance liquid chromatography (RP-HPLC), followed by identification using liquid chromatography–mass spectrometry (LC-MS/MS). Furthermore, based on in silico analysis, one angiotensin-I converting enzyme (ACE)-inhibitory and antioxidant peptide, RGQVIYVL (946.6 Da), and two antioxidant peptides, ASPKPSSA (743.8 Da), and QFLLAGR (803.5 Da), from QBAH were synthesized. RGQVIYVL showed a high ACE-inhibitory activity (IC50 = 38.16 μM) with competitive mode of inhibition, and showed significant antihypertensive effect in spontaneously hypertensive rats at a concentration of 100–150 mg/kg body weight (bw). Molecular docking simulation showed that it could interact with the active ACE site via hydrogen bonds with high binding power. Moreover, RGQVIYVL, ASPKPSSA, and QFLLAGR all demonstrated high ·OH scavenging activity (IC50 = 61.69–117.46 μM), ABTS+ scavenging activity (58.29–74.28%) and Fe2+ chelating ability (32.54–82.48% at 0.5 mg/mL). They could also retain activity after gastrointestinal enzyme digestion. These results indicate that quinoa albumin is a potential source of bioactive peptides possessing antioxidant and ACE-inhibitory activities.

scholarly journals In-silico Molecular Docking and ADME/Pharmacokinetic Prediction Studies of Some Novel Carboxamide Derivatives as Anti-tubercular Agents

2020 ◽  
Vol 3 (4) ◽  
pp. 989-1000
Author(s):  
Mustapha Abdullahi ◽  
Shola Elijah Adeniji
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
In Silico ◽  
Density Functional ◽  
Docking Simulation ◽  
Basis Set ◽  
Hybrid Functional ◽  
Standard Drug

AbstractMolecular docking simulation of thirty-five (35) molecules of N-(2-phenoxy)ethyl imidazo[1,2-a]pyridine-3-carboxamide (IPA) with Mycobacterium tuberculosis target (DNA gyrase) was carried out so as to evaluate their theoretical binding affinities. The chemical structure of the molecules was accurately drawn using ChemDraw Ultra software, then optimized at density functional theory (DFT) using Becke’s three-parameter Lee–Yang–Parr hybrid functional (B3LYP/6-311**) basis set in a vacuum of Spartan 14 software. Subsequently, the docking operation was carried out using PyRx virtual screening software. Molecule 35 (M35) with the highest binding affinity of − 7.2 kcal/mol was selected as the lead molecule for structural modification which led to the development of four (4) newly hypothetical molecules D1, D2, D3 and D4. In addition, the D4 molecule with the highest binding affinity value of − 9.4 kcal/mol formed more H-bond interactions signifying better orientation of the ligand in the binding site compared to M35 and isoniazid standard drug. In-silico ADME and drug-likeness prediction of the molecules showed good pharmacokinetic properties having high gastrointestinal absorption, orally bioavailable, and less toxic. The outcome of the present research strengthens the relevance of these compounds as promising lead candidates for the treatment of multidrug-resistant tuberculosis which could help the medicinal chemists and pharmaceutical professionals in further designing and synthesis of more potent drug candidates. Moreover, the research also encouraged the in vivo and in vitro evaluation study for the proposed designed compounds to validate the computational findings.

scholarly journals Cardiac Rhythm and Molecular Docking Studies of Ion Channel Ligands with Cardiotoxicity in Zebrafish

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 566
Author(s):  
Bonifasius Putera Sampurna ◽  
Fiorency Santoso ◽  
Jia-Hau Lee ◽  
Wen-Hao Yu ◽  
Chin-Chung Wu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Side Effects ◽  
Ion Channel ◽  
In Silico ◽  
Docking Simulation ◽  
Docking Studies ◽  
Zebrafish Model ◽  
Critical Issues ◽  
Domain Iii

Safety is one of the most important and critical issues in drug development. Many drugs were abandoned in clinical trials and retracted from the market because of unknown side effects. Cardiotoxicity is one of the most common reasons for drug retraction due to its potential side effects, i.e., inducing either tachycardia, bradycardia or arrhythmia. The zebrafish model could be used to screen drug libraries with potential cardiotoxicity in a high-throughput manner. In addition, the fundamental principles of replacement, reduction, and refinement of laboratory animal usage, 3R, could be achieved by using zebrafish as an alternative to animal models. In this study, we used a simple ImageJ-based method to evaluate and screen 70 ion channel ligands and successfully identify six compounds with strong cardiotoxicity in vivo. Next, we conducted an in silico-based molecular docking simulation to elucidate five identified compounds that might interact with domain III or domain IV of the Danio rerio L-type calcium channel (LTCC), a known pharmaceutically important target for arrhythmia. In conclusion, in this study, we provide a web lab and dry lab combinatorial approach to perform in vivo cardiotoxicity drug screening and in silico mechanistic studies.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies

2020 ◽  
Vol 20 (3) ◽  
pp. 223-235
Author(s):  
Pooja Shah ◽  
Vishal Chavda ◽  
Snehal Patel ◽  
Shraddha Bhadada ◽  
Ghulam Md. Ashraf
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Reductase Activity ◽  
Infarct Volume ◽  
Docking Studies ◽  
Serum Glucose ◽  
In Vivo Studies ◽  
In Silico Molecular Docking

Background: Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. Objective: The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. Material and Methods: In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. Results: In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. Conclusion: In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

scholarly journals Molecular docking and pharmacokinetic screening of eucalyptol (1,8 cineole) from eucalyptus essential oil against SARS-CoV-2

2020 ◽  
Vol 12 (3) ◽  
pp. 536-545
Author(s):  
Arun D. SHARMA ◽  
Inderjeet KAUR
Keyword(s):  
Molecular Docking ◽  
Essential Oil ◽  
Active Site ◽  
In Silico ◽  
Hydrophobic Interactions ◽  
Rna Virus ◽  
In Silico Analysis ◽  
Active Site Residues ◽  
Virus Family

SARS-CoV-2 (COVID-19), member of corona virus family, is a positive single stranded RNA virus. Due to lack of drugs it is spreading its tentacles across the world. Being associated with cough, fever, and respiratory distress, this disease caused more than 15% mortality worldwide. Mpro/3CLpro has recently been regarded as a suitable target for drug design due to its vital role in virus replication. The current study focused on the inhibitory activity of eucalyptol (1,8 cineole), an essential oil component from eucalyptus oil, against Mpro/3CLprofrom SARS-CoV-2. Till date there is no work is undertaken on in-silico analysis of this compound against Mpro/3CLproof SARS-CoV-2. Molecular docking studies were conducted by using 1-click dock tool and Patchdock analysis. In-silico absorption, distribution, metabolism, excretion and toxicity (ADMET) profile were also studied. The calculated parameters such as docking score indicated effective binding of eucalyptol to COVID-19 Mpro protein. Active site prediction revealed the involvement of active site residues in ligand binding. Interactions results indicated that, Mpro/3CLpro/eucalyptol complexes forms hydrophobic interactions. ADMET studies provided guidelines and mechanistic scope for identification of potent anti-COVID 19 drug. Therefore, eucalyptol may represent potential herbal treatment to act as COVID-19 Mpro/3CLproinhibitor, a finding which must be validated in vivo.

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