scholarly journals ANALYSIS OF MOLECULAR DOCKING EFFICIENCY OF CLEISTANTHIN-A, AS AN ALTERNATIVE FOR NICOTINE ADDICTION

2018 ◽  
Vol 10 (4) ◽  
pp. 98
Author(s):  
A. Amala Lourthuraj ◽  
M. Masilamani Selvam ◽  
Bharathi Ravikrishnan ◽  
M. Vinoth ◽  
Waheeta Hopper
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Protein Data Bank ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
High Throughput ◽  
In Silico ◽  
Data Bank ◽  
Tobacco Consumption ◽  
Nicotinic Acetylcholine

Objective: The present research was aimed to understand the molecular docking efficiency of a plant-derived compound cleistanthin-A and a common ingredient in tobacco consumption nicotine with nicotinic acetylcholine receptor (nAChR).Methods: The 3-D structure of nAChR was retrieved from the protein data bank (ID 5AFH). Ligand was obtained from the PUBCHEM. The in silico protocol comprised of three steps: high-throughput virtual screening (HTVS), standard preci­sion (SP) and extra precision (XP). The screened molecules were ranked accordingly using glide score. Schrödinger tool was used to perform the docking analysis.Results: The binding efficiency of the nicotine and cleistanthin-A was found to be docked at the cys-cys loop of the receptor. Based upon the glide score and glide energy it can be reported that, nicotine binding can be inhibited by the binding of cleistanthin-A to the nAChR.Conclusion: The docking efficiency of cleistanthin-A was good compared to nicotine towards nAChR. Hence, cleistanthin–A was derived as a better choice as an alternative for nicotine in smoke therapy.

scholarly journals IN SILICO DESIGN AND MOLECULAR DOCKING STUDIES OF SOME 1, 2-BENZISOXAZOLE DERIVATIVES FOR THEIR ANALGESIC AND ANTI-INFLAMMATORY ACTIVITY

2017 ◽  
Vol 9 (3) ◽  
pp. 133
Author(s):  
Sarath Sasi Kumar ◽  
Anjali T
Keyword(s):  
Molecular Docking ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Analgesic Activity ◽  
In Silico ◽  
Docking Studies ◽  
Inflammatory Activity ◽  
Nicotinic Acetylcholine ◽  
Cox 2 ◽  
Anti Inflammatory

Objective: In silico design and molecular docking of 1,2-benzisoxazole derivatives for their analgesic and anti-inflammatory activity using computational methods.Methods: In silico molecular properties of 1,2-benzisoxazole derivatives were predicted using various software’s such as Chemsketch, Molinspiration, PASS and Schrodinger to select compounds having optimum drug-likeness, molecular descriptors resembling those of standard drugs and not violating the ‘Lipinski rule of 5’. Molecular docking was performed on active site of nicotinic acetylcholine receptor (PDB: 2KSR) for analgesic activity and COX-2 (PDB: 6COX) for anti-inflammatory activity using Schrodinger under maestro molecular modelling environment.Results: From the results of molecular docking studies of 1,2-benzisoxazole derivatives, all the compounds showed good binding interactions with Nicotinic acetylcholine receptor and COX-2. Compounds 4a and 4c showed highest binding scores (-7.46 and-7.21 respectively) with nicotinic acetylcholine receptor and exhibited maximum analgesic activity. Compound 4a showed highest binding score (-7.8) with COX-2 and exhibited maximum anti-inflammatory activity.Conclusion: All the derivatives of 1,2-benzisoxazole showed good analgesic and anti-inflammatory activity as predicted using molecular docking on respective receptors.

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 In Silico Finding of Key Interaction Mediated α3β4 and α7 Nicotinic Acetylcholine Receptor Ligand Selectivity of Quinuclidine-Triazole Chemotype

2020 ◽  
Vol 21 (17) ◽  
pp. 6189
Author(s):  
Kuntarat Arunrungvichian ◽  
Sumet Chongruchiroj ◽  
Jiradanai Sarasamkan ◽  
Gerrit Schüürmann ◽  
Peter Brust ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
In Silico ◽  
Amino Acid Residues ◽  
Nicotinic Acetylcholine ◽  
Selective Binding ◽  
Ligand Selectivity ◽  
Α7 Nachr ◽  
Nachr Subtype

The selective binding of six (S)-quinuclidine-triazoles and their (R)-enantiomers to nicotinic acetylcholine receptor (nAChR) subtypes α3β4 and α7, respectively, were analyzed by in silico docking to provide the insight into the molecular basis for the observed stereospecific subtype discrimination. Homology modeling followed by molecular docking and molecular dynamics (MD) simulations revealed that unique amino acid residues in the complementary subunits of the nAChR subtypes are involved in subtype-specific selectivity profiles. In the complementary β4-subunit of the α3β4 nAChR binding pocket, non-conserved AspB173 through a salt bridge was found to be the key determinant for the α3β4 selectivity of the quinuclidine-triazole chemotype, explaining the 47–327-fold affinity of the (S)-enantiomers as compared to their (R)-enantiomer counterparts. Regarding the α7 nAChR subtype, the amino acids promoting a however significantly lower preference for the (R)-enantiomers were the conserved TyrA93, TrpA149 and TrpB55 residues. The non-conserved amino acid residue in the complementary subunit of nAChR subtypes appeared to play a significant role for the nAChR subtype-selective binding, particularly at the heteropentameric subtype, whereas the conserved amino acid residues in both principal and complementary subunits are essential for ligand potency and efficacy.

scholarly journals Effects of nicotinic acetylcholine receptor-activating alkaloids on anxiety-like behavior in zebrafish

2021 ◽  
Author(s):  
Ainhoa Alzualde ◽  
Oihane Jaka ◽  
Diogo A. R. S. Latino ◽  
Omar Alijevic ◽  
Iñaki Iturria ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
In Silico ◽  
Biological Activities ◽  
Nicotinic Acetylcholine ◽  
Diverse Range ◽  
In Silico Docking ◽  
Docking Model ◽  
Behavioral Paradigm

AbstractAlkaloids are a structurally complex group of natural products that have a diverse range of biological activities and significant therapeutic applications. In this study, we examined the acute, anxiolytic-like effects of nicotinic acetylcholine receptor (nAChR)-activating alkaloids with reported neuropharmacological effects but whose effects on anxiety are less well understood. Because α4β2 nAChRs can regulate anxiety, we first demonstrated the functional activities of alkaloids on these receptors in vitro. Their effects on anxiety-like behavior in zebrafish were then examined using the zebrafish novel tank test (NTT). The NTT is a relatively high-throughput behavioral paradigm that takes advantage of the natural tendency of fish to dive down when stressed or anxious. We report for the first time that cotinine, anatabine, and methylanatabine may suppress this anxiety-driven zebrafish behavior after a single 20-min treatment. Effective concentrations of these alkaloids were well above the concentrations naturally found in plants and the concentrations needed to induce anxiolytic-like effect by nicotine. These alkaloids showed good receptor interactions at the α4β2 nAChR agonist site as demonstrated by in vitro binding and in silico docking model, although somewhat weaker than that for nicotine. Minimal or no significant effect of other compounds may have been due to low bioavailability of these compounds in the brain, which is supported by the in silico prediction of blood–brain barrier permeability. Taken together, our findings indicate that nicotine, although not risk-free, is the most potent anxiolytic-like alkaloid tested in this study, and other natural alkaloids may regulate anxiety as well.

scholarly journals DOCKING MOLEKULER SENYAWA METABOLIT SEKUNDER Lantana camara SEBAGAI ANTIINFLAMASI TERHADAP ENZIM COX-1

Jurnal Biota ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. 79-83
Author(s):  
Atim Febry Masula ◽  
Dian Puspitasari ◽  
Eili Supriatin S.W ◽  
Khoirul Ummah ◽  
Dinik Rokhmatin ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Protein Data Bank ◽  
In Silico ◽  
Data Bank ◽  
Lantana Camara ◽  
Lantadene A ◽  
Cox 1

Lantana camara mengandung beberapa jenis flavonoid seperti Umuhengerin, Lantadene A, Lantadene B, Ictero -genin. Salah satu mekanisme kerja flavonoid sebagai antiinflammatoryis dengan menghambat ceptor siklooksigenase (COX). Penelitian ini bertujuan untuk mengetahui afinitas senyawa flavonoid yang terkandung dalam L. camara dengan reseptor COX-1 sebagai antiinflamasi dan untuk mengetahui ikatan hidrogen yang dapat dibentuk dengan metode molecular docking. Pengujian in silico dilakukan berdasarkan metode desain obat yang dibantu komputer. Alat-alat yang digunakan dalam penelitian ini, perangkat lunak PyRx, perangkat lunak PyMol, Pubchem (senyawa database), PDB (Protein Data Bank), dan Po-seView. Berdasarkan hasil docking dan pembahasan di atas dapat disimpulkan bahwa Icterogenin com-pound dan senyawa Umuhengerin adalah senyawa yang paling efektif dalam proses antiinflamasi, Icterogenin com-pound memiliki nilai RMSD 41,1 Å dan nilai afinity mengikat -8,8 dan senyawa Umuhengerin memiliki val-ue RMSD 1, 61 Å dan nilai afinitas pengikatan -8.0. Ini menunjukkan bahwa senyawa tersebut memiliki nilai RMSD dari senyawa Icterogenin. Namun, senyawa Icterogenin memiliki ikatan hidrogen yang lebih kuat dan lebih efisien daripada senyawa Umuhengerin karena nilai afinitas pengikatan terendah.

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