scholarly journals Molecular Docking and In Silico ADMET Study Reveals Acylguanidine 7a as a Potential Inhibitor of β-Secretase

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Chaluveelaveedu Murleedharan Nisha ◽  
Ashwini Kumar ◽  
Prateek Nair ◽  
Nityasha Gupta ◽  
Chitrangda Silakari ◽  
...  
Keyword(s):  
Binding Energy ◽  
Tartaric Acid ◽  
In Silico ◽  
Data Bank ◽  
Positive Control ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Promising Target ◽  
In Silico Admet ◽  
As Solubility

Amyloidogenic pathway in Alzheimer’s disease (AD) involves breakdown of APP by β-secretase followed by γ-secretase and results in formation of amyloid beta plaque. β-secretase has been a promising target for developing novel anti-Alzheimer drugs. To test different molecules for this purpose, test ligands like acylguanidine 7a, rosiglitazone, pioglitazone, and tartaric acid were docked against our target protein β-secretase enzyme retrieved from Protein Data Bank, considering MK-8931 (phase III trial, Merck) as the positive control. Docking revealed that, with respect to their free binding energy, acylguanidine 7a has the lowest binding energy followed by MK-8931 and pioglitazone and binds significantly to β-secretase. In silico ADMET predictions revealed that except tartaric acid all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics. These compounds may serve as potential lead compound for developing new anti-Alzheimer drug.

scholarly journals IN SILICO STUDY OF ARYL EUGENOL DERIVATIVES AS ANTI-COLORECTAL CANCER BY INDUCING OF APOPTOSIS

2017 ◽  
Vol 10 (12) ◽  
pp. 345
Author(s):  
Fadilah Fadilah ◽  
Arry Yanuar ◽  
Ade Arsianti ◽  
Retnosari Andrajati ◽  
Erni Hernawati Purwaningsih
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Computer Software ◽  
Data Bank ◽  
The Body ◽  
Software Applications ◽  
In Silico Admet ◽  
In Silico Study ◽  
Abnormal Cells ◽  
Cancer Tissues

Objective: Apoptosis is one method the body uses to get rid of unneeded or abnormal cells, but cancer cells have strategies to avoid apoptosis. Apoptosis inducers can get around these strategies to cause the death of cancer cells.Methods: We screened some derivatives aryl eugenol based on their interactions with Bcl-2 in many cancer tissues, using computer software applications (in silico method) to determine the best compounds. The docking experiment on Bcl-2 (Protein Data Bank ID 4LXD) was carried out by suitably positioning the energy-minimized ligand in the active site while carefully monitoring non-bonded interactions of the ligand enzyme.Results: The resulting ligand-receptor complex was docked using the Autodock Vina software. Docking results based free binding energy, EUGACl (21), EUASABr (17), EUGEABr (19), and EUASACL (17), has the lowest binding energy than navitoclax and binds significantly to BCL 2. In silico ADMET predictions revealed that except SA, ASA, and GEA, all other compounds had minimal toxic effects and had good absorption as well as solubility characteristics.Conclusion: These compounds of aryl eugenol (17, 19, and 21) may serve as a potential lead compound for developing new anticancer as apoptosis inducers.

Virtual Screening, Molecular docking and in-silico ADME-Tox analysis for identification of potential main protease (Mpro) enzyme inhibitors

2020 ◽  
Vol 18 ◽  
Author(s):  
Debadash Panigrahi ◽  
Ganesh Prasad Mishra
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
In Silico ◽  
Data Bank ◽  
Future Research ◽  
Reference Compound ◽  
Unexpected Death ◽  
Main Protease ◽  
In Silico Admet

Objective:: Recent pandemic caused by SARS-CoV-2 described in Wuhan China in December-2019 spread widely almost all the countries of the world. Corona virus (COVID-19) is causing the unexpected death of many peoples and severe economic loss in several countries. Virtual screening based on molecular docking, drug-likeness prediction, and in silico ADMET study has become an effective tool for the identification of small molecules as novel antiviral drugs to treat diseases. Methods:: In the current study, virtual screening was performed through molecular docking for identifying potent inhibitors against Mpro enzyme from the ZINC library for the possible treatment of COVID-19 pandemic. Interestingly, some compounds are identified as possible anti-covid-19 agents for future research. 350 compounds were screened based on their similarity score with reference compound X77 from ZINC data bank and were subjected to docking with crystal structure available of Mpro enzyme. These compounds were then filtered by their in silico ADME-Tox and drug-likeness prediction values. Result:: Out of these 350 screened compounds, 10 compounds were selected based on their docking score and best docked pose in comparison to the reference compound X77. In silico ADME-Tox and drug likeliness predictions of the top compounds were performed and found to be excellent results. All the 10 screened compounds showed significant binding pose with the target enzyme main protease (Mpro) enzyme and satisfactory pharmacokinetic and toxicological properties. Conclusion:: Based on results we can suggest that the identified compounds may be considered for therapeutic development against the COVID-19 virus and can be further evaluated for in vitro activity, preclinical, clinical studies and formulated in a suitable dosage form to maximize their bioavailability.

scholarly journals A phase III trial to evaluate the efficacy, fabric integrity and community acceptance of Netprotect® using a recommended long-lasting insecticidal net as positive control

2014 ◽  
Vol 13 (1) ◽  
pp. 256 ◽  
Author(s):  
Karel Van Roey ◽  
Siv Sovannaroth ◽  
Tho Sochantha ◽  
Mao Touch ◽  
Olivier Pigeon ◽  
...  
Keyword(s):  
Positive Control ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Community Acceptance ◽  
Fabric Integrity

scholarly journals In Silico Study on Interaction and Preliminary Toxicity Prediction of Eleutherine americana Components as an Antifungal and Antitoxoplasmosis Candidate

2020 ◽  
Vol 20 (4) ◽  
pp. 899
Author(s):  
Sophi Damayanti ◽  
Nadiyah Athifah Salim Martak ◽  
Benny Permana ◽  
Adi Suwandi ◽  
Rika Hartati ◽  
...  
Keyword(s):  
Binding Energy ◽  
In Silico ◽  
Aquatic Toxicity ◽  
Three Dimensional ◽  
Positive Control ◽  
Toxicity Prediction ◽  
Target Proteins ◽  
Discovery Studio ◽  
Free Binding Energy ◽  
Eleutherine Americana

Red bulbs of Eleutherine americana (Aubl.) Merr. ex K. Heyne has been known for its high content of naphthoquinones that have antifungal and antiparasitic activities. In this research, in silico interaction study was performed between 31 compounds reported to be found in E. americana with the selected target proteins for antifungal and antitoxoplasmosis activity using the molecular docking method. An ORPs (OSBP-related proteins), Osh4 (PDB ID: 1ZHX), and N-myristoyltransferase (Nmt, PDB ID: 1IYL) were used as the antifungal target proteins. Toxoplasma gondii purine nucleoside phosphorylase (TgPNP, PDB ID: 3MB8) and calcium-dependent protein kinase-1 (TgCDPK1, PDB ID: 4M84) were used as antitoxoplasmosis target proteins. Three-dimensional structures of the test compounds were made and optimized using GaussView 6.0 and Gaussian 09W. The target proteins were prepared using the Discovery Studio 2016 Program. Aquatic toxicity prediction as the preliminary assessment of the safety of the compounds was performed using ECOSAR v2.0. The results suggest that the compound having both the smallest free binding energy compared with positive control and other test compounds and low predicted toxicity is β-sitosterol with a free binding energy of ‒11.55 and ‒11.18 kcal/mol towards Osh4 and Nmt and ‒8.06 and ‒10.29 kcal/mol towards TgPNP and TgCDPK1, respectively.

scholarly journals In silico studies of selected xanthophylls as potential candidates against SARS-CoV-2 targeting main protease (Mpro) and papain-like protease (PLpro)

2021 ◽  
Vol 67 (2) ◽  
pp. 1-8
Author(s):  
Tomasz M. Karpiński ◽  
Marek Kwaśniewski ◽  
Marcin Ożarowski ◽  
Rahat Alam
Keyword(s):  
Binding Energy ◽  
Active Site ◽  
In Silico ◽  
Active Sites ◽  
Data Bank ◽  
Pharmacokinetic Parameters ◽  
Discovery Studio ◽  
Main Protease ◽  
In Silico Studies ◽  
Potential Inhibitors

Summary Introduction: The main protease (Mpro) and the papain-like protease (PLpro) are essential for the replication of SARS-CoV-2. Both proteases can be targets for drugs acting against SARS-CoV-2. Objective: This paper aims to investigate the in silico activity of nine xanthophylls as inhibitors of Mpro and PLpro. Methods: The structures of Mpro (PDB-ID: 6LU7) and PLpro (PDB-ID: 6W9C) were obtained from RCSB Protein Data Bank and developed with BIOVIA Discovery Studio. Active sites of proteins were performed using CASTp. For docking the PyRx was used. Pharmacokinetic parameters of ADMET were evaluated using SwissADME and pkCSM. Results: β-cryptoxanthin exhibited the highest binding energy: –7.4 kcal/mol in the active site of Mpro. In PLpro active site, the highest binding energy had canthaxanthin of –9.4 kcal/mol, astaxanthin –9.3 kcal/mol, flavoxanthin –9.2 kcal/mol and violaxanthin –9.2 kcal/mol. ADMET studies presented lower toxicity of xanthophylls in comparison to ritonavir and ivermectin. Conclusion: Our findings suggest that xanthophylls can be used as potential inhibitors against SARS-CoV-2 main protease and papain-like protease.

scholarly journals In silico docking analysis of CCL28 (C-C motif chemokine ligand 28) and astragalin as the potential inhibitor of rheumatoid arthritis

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 313
Author(s):  
Sadaf Noor ◽  
Syeda Tahira Qousain ◽  
Syed Aun Muhammad
Keyword(s):  
Rheumatoid Arthritis ◽  
Binding Energy ◽  
Binding Affinity ◽  
In Silico ◽  
Joint Inflammation ◽  
Black Tea ◽  
Data Bank ◽  
Dimensional Structure ◽  
In Silico Docking ◽  
Chemokine Ligand

Background: Rheumatoid arthritis is an inflammatory and chronic disease of the joints affecting 1% of the world’s population. Women are three times more likely to be affected than men. Many drugs are being used for the treatment of rheumatoid arthritis but they often have severe side effects. C-C motif chemokine ligand 28 (CCL28) recruits leukocytes and other proinflammatory factors to the site of joint inflammation. The purpose of the present research is the computational evaluation of astragalin, a natural flavonoid extracted from black tea, as an inhibitor of CCL28 by in silico docking.   Methods: The three-dimensional structure of CCL28 to act as a molecular target was obtained from the Protein Data Bank (PDB ID: 6CWS). The quality of the CCL28 structure was assessed using Phyre2 and Molecular Operating Environment (MOE) software was used for binding affinity analysis. Astragalin served as a ligand for docking and naproxen, a known drug for rheumatoid arthritis, was used as a standard for comparison. Results: In molecular docking, astragalin showed significant binding affinity with the CCL28 target molecule, with a binding energy of -5.40 kcal/mol, in comparison with naproxen which has a binding energy of -4.87 kcal/mol. Astragalin has strong binding affinity for CCL28 as compared to standard naproxen. Conclusion: This study revealed that astragalin could have the potential to serve as an inhibitor of CCL28 for the treatment of rheumatoid arthritis.

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