In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

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New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180326152726 ◽

2018 ◽

Vol 16 (1) ◽

pp. 82-92 ◽

Cited By ~ 1

Author(s):

Ahmet Özdemir ◽

Belgin Sever ◽

Mehlika Dilek Altıntop

Keyword(s):

In Silico ◽

Fungal Infections ◽

Computational Study ◽

Docking Studies ◽

In Vivo Studies ◽

Heme Group ◽

In Silico Studies ◽

Nih 3T3

Background: Azoles are commonly used in the treatment and prevention of fungal infections. They suppress fungal growth by acting on the heme group of lanosterol 14α-demethylase enzyme (CYP51), thus blocking the biosynthesis of ergosterol. Objectives: Due to the importance of pyrazolines in the field of antifungal drug design, we aimed to design and synthesize new pyrazoline-based anticandidal agents. Methods: New pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2- thienyl)-5-(1,3-benzodioxol-5-yl)-2-pyrazoline with aryl thiols. These compounds were evaluated for their in vitro antifungal effects on Candida species. Docking studies were performed to predict the affinity of the most effective anticandidal agents to substrate binding site of CYP51. Furthermore, MTT assay was performed to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. A computational study for the prediction of ADME properties of all compounds was also carried out. Results: Compounds 5, 8, 10 and 12 were found as the most potent anticandidal agents against Candida albicans and Candida glabrata in this series with the same MIC values of ketoconazole and they also exhibited low toxicity against NIH/3T3 cells. Docking results indicated that all these compounds showed good binding affinity into the active site of CYP51. In particular, chloro substituted compounds 8 and 12 bind to CYP51 through direct coordination with the heme group. According to in silico studies, compound 8 only violated one parameter of Lipinski’s rule of five, making it a potential orally bioavailable agent. Conclusion: Compound 8 was defined as a promising candidate for further in vitro and in vivo studies.

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Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

Current Pharmaceutical Design ◽

10.2174/1381612826666201112143230 ◽

2020 ◽

Vol 26 ◽

Author(s):

John Chen ◽

Andrew Martin ◽

Warren H. Finlay

Keyword(s):

Drug Delivery ◽

In Silico ◽

Local Drug Delivery ◽

In Vivo Studies ◽

Intranasal Drug Delivery ◽

Nasal Sprays ◽

In Silico Studies ◽

Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

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[18F]Amylovis as a Potential PET Probe for β-Amyloid Plaque: Synthesis, In Silico, In vitro and In vivo Evaluations

Current Radiopharmaceuticals ◽

10.2174/1874471012666190102165053 ◽

2019 ◽

Vol 12 (1) ◽

pp. 58-71 ◽

Cited By ~ 2

Author(s):

Suchitil Rivera-Marrero ◽

Laura Fernández-Maza ◽

Samila León-Chaviano ◽

Marquiza Sablón-Carrazana ◽

Alberto Bencomo-Martínez ◽

...

Keyword(s):

In Silico ◽

Specific Activity ◽

Senile Plaques ◽

Coupling Reaction ◽

In Vitro Assays ◽

Mice Model ◽

Wild Mice ◽

In Silico Studies

Background: Alzheimer’s disease (AD) is the most common form of dementia. Neuroimaging methods have widened the horizons for AD diagnosis and therapy. The goals of this work are the synthesis of 2-(3-fluoropropyl)-6-methoxynaphthalene (5) and its [18F]-radiolabeled counterpart ([18F]Amylovis), the in silico and in vitro comparative evaluations of [18F]Amylovis and [11C]Pittsburg compound B (PIB) and the in vivo preclinical evaluation of [18F]Amylovis in transgenic and wild mice. Methods: Iron-catalysis cross coupling reaction, followed by fluorination and radiofluorination steps were carried out to obtain 5 and 18F-Amylovis. Protein/Aß plaques binding, biodistribution, PET/CT Imaging and immunohistochemical studies were conducted in healthy/transgenic mice. Results: The synthesis of 5 was successful obtained. Comparative in silico studies predicting that 5 should have affinity to the Aβ-peptide, mainly through π-π interactions. According to a dynamic simulation study the ligand-Aβ peptide complexes are stable in simulation-time (ΔG = -5.31 kcal/mol). [18F]Amylovis was obtained with satisfactory yield, high radiochemical purity and specific activity. The [18F]Amylovis log Poct/PBS value suggests its potential ability for crossing the blood brain barrier (BBB). According to in vitro assays, [18F]Amylovis has an adequate stability in time. Higher affinity to Aβ plaques were found for [18F]Amylovis (Kd 0.16 nmol/L) than PIB (Kd 8.86 nmol/L) in brain serial sections of 3xTg-AD mice. Biodistribution in healthy mice showed that [18F]Amylovis crosses the BBB with rapid uptake (7 %ID/g at 5 min) and good washout (0.11±0.03 %ID/g at 60 min). Comparative PET dynamic studies of [18F]Amylovis in healthy and transgenic APPSwe/PS1dE9 mice, revealed a significant high uptake in the mice model. Conclusion: The in silico, in vitro and in vivo results justify that [18F]Amylovis should be studied as a promissory PET imaging agent to detect the presence of Aβ senile plaques.

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In Silico Analysis and Molecular Docking Studies of Plumbagin and Piperine Ligands as Potential Inhibitors of Alpha-Glucosidase Receptor

Biointerface Research in Applied Chemistry ◽

10.33263/briac112.96299637 ◽

2020 ◽

Vol 11 (2) ◽

pp. 9629-9637

Keyword(s):

In Silico ◽

In Silico Analysis ◽

Docking Studies ◽

The Body ◽

Insufficient Amount ◽

In Silico Studies ◽

Optimization Simulation ◽

Alpha Glucosidase

In ’today’s generation, Diabetes mellitus is a very common lifestyle-based disease in which an insufficient amount of insulin is produced, which results in a rise of glucose level in the body with frequent urination and patient feels thirsty and hungry. In our present work, we have used the alpha-glucosidase receptor against the natural plant product as a ligand for docking studies. For this in silico studies, various online tools, databases, and software were used. The proposed approaches were PDB, Molinspiration, Chemsketch, PyRx software, and many more. The binding scores were retrieved by PyRx software and no tumorigenicity, mutagenicity was there, and all parameters were in the desired range. The compounds used as ligands have shown energy minimization up to -6.7 to -8.7 kcal and can be further used as optimization, simulation, and in vitro and in vivo experimental validation.

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Natural Products as Potential Agents Against SARS-CoV and SARS-CoV-2

Current Medicinal Chemistry ◽

10.2174/0929867328666210125113938 ◽

2021 ◽

Vol 28 ◽

Author(s):

Joanda Paolla Raimundo e Silva ◽

Chonny Alexander Herrera Acevedo ◽

Thalisson Amorim de Souza ◽

Renata Priscila Barros de Menezes ◽

Zoe L. Sessions ◽

...

Keyword(s):

Natural Products ◽

In Silico ◽

Principal Component ◽

In Vivo Studies ◽

In Vitro Assays ◽

Future Research ◽

Natural Substances ◽

Effective Drugs

Background: Natural products are useful agents for the discovery of new lead-compounds and effective drugs to combat coronaviruses (CoV). Objective: The present work provides an overview of natural substances, plant extracts, and essential oils as potential antiSARS-CoV agents. In addition, this work evaluates their drug-like properties which are essential in the selection of compounds in order to accelerate the drug development process. Methods: The search was carried out using PubMed, ScienceDirect and SciFinder. Articles addressing plant-based natural products as potential SARS-CoV or SARS-CoV-2 agents within the last seventeen years were analyzed and selected. The descriptors for Chemometrics analyzes were obtained in alvaDesc and the principal component analyzes (PCA) were carried out in SIMCA version 13.0. Results: Based on in vitro assays and computational analyzes, this review covers twenty nine medicinal plant species and more than 300 isolated substances as potential anti-coronavirus agents. Among them, flavonoids and terpenes were the most promising compound classes. In silico analyses of drug-like properties corroborate these findings and indicate promising candidates for in vitro and in vivo studies to validate their activity. Conclusion: This paper highlights the role of ethnopharmacology in drug discovery and simulates the use of integrative (in silico/ in vitro) and chemocentric approaches to strengthen current studies and guide future research in the field of antivirals agents.

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In silico Exploration of Bioactive Phytochemicals Against Neurodegenerative Diseases Via Inhibition of Cholinesterases

Current Pharmaceutical Design ◽

10.2174/1381612826666200316125517 ◽

2020 ◽

Vol 26 (33) ◽

pp. 4151-4162 ◽

Cited By ~ 1

Author(s):

Fawzi Mahomoodally ◽

Hassan H. Abdallah ◽

Shanoo Suroowan ◽

Sharmeen Jugreet ◽

Yansheng Zhang ◽

...

Keyword(s):

Neurodegenerative Disorders ◽

In Silico ◽

Randomized Clinical Trials ◽

Synaptic Cleft ◽

Docking Studies ◽

In Vivo Studies ◽

In Silico Docking ◽

Long Term Treatment

Neurodegenerative disorders are estimated to become the second leading cause of death worldwide by 2040. Despite the widespread use of diverse allopathic drugs, these brain-associated disorders can only be partially addressed and long term treatment is often linked with dependency and other unwanted side effects. Nature, believed to be an arsenal of remedies for any illness, presents an interesting avenue for the development of novel neuroprotective agents. Interestingly, inhibition of cholinesterases, involved in the breakdown of acetylcholine in the synaptic cleft, has been proposed to be neuroprotective. This review therefore aims to provide additional insight via docking studies of previously studied compounds that have shown potent activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro. Indeed, the determination of potent plant-based ligands for this purpose through in silico methods enables the elimination of lengthy and costly traditional methods of drug discovery. Herein, a literature search was conducted to identify active phytochemicals which are cholinesterase inhibitors. Following which in silico docking methods were applied to obtain docking scores. Compound structures were extracted from online ZINC database and optimized using AM1 implemented in gaussian09 software. Noteworthy ligands against AChE highlighted in this study include: 19,20-dihydroervahanine A and 19, 20-dihydrotabernamine. Regarding BChE inhibition, the best ligands were found to be 8-Clavandurylkaempferol, Na-methylepipachysamine D; ebeiedinone; and dictyophlebine. Thus, ligand optimization between such phytochemicals and cholinesterases coupled with in vitro, in vivo studies and randomized clinical trials can lead to the development of novel drugs against neurodegenerative disorders.

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Unraveling the Antioxidant, Binding and Health-Protecting Properties of Phenolic Compounds of Beers with Main Human Serum Proteins: In Vitro and In Silico Approaches

Molecules ◽

10.3390/molecules25214962 ◽

2020 ◽

Vol 25 (21) ◽

pp. 4962

Author(s):

Raja Mohamed Beema Shafreen ◽

Selvaraj Alagu Lakshmi ◽

Shunmugiah Karutha Pandian ◽

Yong Seo Park ◽

Young Mo Kim ◽

...

Keyword(s):

Human Serum ◽

In Silico ◽

Serum Proteins ◽

In Silico Analysis ◽

Cardiovascular Effects ◽

In Vivo Studies ◽

In Silico Studies ◽

Human Serum Proteins

Our recently published in vivo studies and growing evidence suggest that moderate consumption of beer possesses several health benefits, including antioxidant and cardiovascular effects. Although beer contains phenolic acids and flavonoids as the major composition, and upon consumption, the levels of major components increase in the blood, there is no report on how these beer components interact with main human serum proteins. Thus, to address the interaction potential between beer components and human serum proteins, the present study primarily aims to investigate the components of beer from different industrial sources as well as their mode of interaction through in silico analysis. The contents of the bioactive compounds, antioxidant capacities and their influence on binding properties of the main serum proteins in human metabolism (human serum albumin (HSA), plasma circulation fibrinogen (PCF), C-reactive protein (CRP) and glutathione peroxidase 3 (GPX3)) were studied. In vitro and in silico studies indicated that phenolic substances presented in beer interact with the key regions of the proteins to enhance their antioxidant and health properties. We hypothesize that moderate consumption of beer could be beneficial for patients suffering from coronary artery disease (CAD) and other health advantages by regulating the serum proteins.

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Protease Inhibitory Effect of Natural Polyphenolic Compounds on SARS-CoV-2: An In Silico Study

Molecules ◽

10.3390/molecules25204604 ◽

2020 ◽

Vol 25 (20) ◽

pp. 4604

Author(s):

Rajveer Singh ◽

Anupam Gautam ◽

Shivani Chandel ◽

Arijit Ghosh ◽

Dhritiman Dey ◽

...

Keyword(s):

In Silico ◽

Inhibitory Effect ◽

Polyphenolic Compounds ◽

Host Protein ◽

In Vivo Studies ◽

Pharmacokinetic Parameters ◽

Post Translational Modification ◽

In Silico Studies

The current pandemic, caused by SARS-CoV-2 virus, is a severe challenge for human health and the world economy. There is an urgent need for development of drugs that can manage this pandemic, as it has already infected 19 million people and led to the death of around 711,277 people worldwide. At this time, in-silico studies are providing lots of preliminary data about potential drugs, which can be a great help in further in-vitro and in-vivo studies. Here, we have selected three polyphenolic compounds, mangiferin, glucogallin, and phlorizin. These compounds are isolated from different natural sources but share structural similarities and have been reported for their antiviral activity. The objective of this study is to analyze and predict the anti-protease activity of these compounds on SARS-CoV-2main protease (Mpro) and TMPRSS2 protein. Both the viral protein and the host protein play an important role in the viral life cycle, such as post-translational modification and viral spike protein priming. This study has been performed by molecular docking of the compounds using PyRx with AutoDock Vina on the two aforementioned targets chosen for this study, i.e., SARS-CoV-2 Mpro and TMPRSS2. The compounds showed good binding affinity and are further analyzed by (Molecular dynamic) MD and Molecular Mechanics Poisson-Boltzmann Surface Area MM-PBSA study. The MD-simulation study has predicted that these natural compounds will have a great impact on the stabilization of the binding cavity of the Mpro of SARS-CoV-2. The predicted pharmacokinetic parameters also show that these compounds are expected to have good solubility and absorption properties. Further predictions for these compounds also showed no involvement in drug-drug interaction and no toxicity.

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

Current Gene Therapy ◽

10.2174/1566523220999200726225457 ◽

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.

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