Activity modeling, molecular docking and pharmacokinetic studies of some boron-pleuromutilins as anti-wolbachia agents with potential for treatment of filarial diseases

2021 ◽  
pp. 100783
Author(s):  
Fabian A. Ugbe ◽  
Gideon A. Shallangwa ◽  
Adamu Uzairu ◽  
Ibrahim Abdulkadir
Keyword(s):  
Molecular Docking ◽  
Pharmacokinetic Studies ◽  
Activity Modeling

scholarly journals Ameliorative Role of Nutraceutical Quercetin and its Derivatives Against Cognitive Impairment Process Induced by Lead Exposure in Drosophila melanogaster(Fruit Fly)

2021 ◽  
Vol 30 (2) ◽  
pp. 135-142
Author(s):  
Abubakar lema Abdullahi ◽  
A. A. Lema ◽  
K. Jibrin ◽  
W. Nuraddeen ◽  
E. M. Alexander
Keyword(s):  
Drosophila Melanogaster ◽  
Molecular Docking ◽  
Therapeutic Index ◽  
Fruit Fly ◽  
Acetylcholinesterase Activity ◽  
Docking Studies ◽  
Pharmacokinetic Studies ◽  
Glutathione S Transferase ◽  
High Therapeutic Index ◽  
In Silico Toxicity

Cumulative lifetime lead (Pb) exposure has been associated with accelerated declines in cognition through the free radical generation and epigenetic effects. Several pieces of literature have identified a correlation between exposure to lead and neurodegenerative disorders. Harwich strain Drosophila melanogaster was exposed to lead acetate for two weeks, and changes in pulse transmission by acetylcholinesterase and systemic redox were evaluated. Besides, molecular docking studies of acetylcholinesterase against Quercetin and its most common derivatives contained in food have been performed. Pharmacokinetic studies on Quercetin and its derivatives have also been performed in silico toxicity. The data obtained showed alterations in antioxidant enzymes and molecules such as catalase, glutathione-S-transferase, and glutathione. Upregulation of acetylcholinesterase activity was observed after treatment with Quercetin. In molecular docking tests, Quercetin and its derivatives were found to bind to acetylcholinesterase's active and peripheral pockets. Pharmacokinetic studies demonstrate moderate solubility, high therapeutic index, excellent absorption potential, hepatoprotective and non-mutagenic properties. With other antioxidant molecules, Quercetin may also play a crucial role in avoiding the development of Alzheimer's and associated antioxidant disorders.  

scholarly journals Physiochemical, molecular docking, and pharmacokinetic studies of Naproxen and its modified derivatives based on DFT

2018 ◽  
Vol 6 (09) ◽  
Author(s):  
Monir Uzzaman ◽  
Mohammed Jabedul Hoque
Keyword(s):  
Molecular Docking ◽  
Binding Affinity ◽  
Density Functional ◽  
Parent Drug ◽  
Electronic Energy ◽  
Frontier Molecular Orbital ◽  
Pharmacokinetic Studies ◽  
Biochemical Interaction ◽  
Gibb’S Free Energy ◽  
Anti Inflammation

Naproxen (N) is a member of nonsteroidal anti-inflammation drug and widely used as an analgesic, antipyretic, and anti-inflammation agent. In this investigation, the inherent stability and biochemical interaction of Naproxen and its related molecules have been studied. Density functional theory (DFT) with B3LYP/ 6-31G (d, p) has been employed to optimize the structures. Frontier molecular orbital features (HOMO-LUMO gap, hardness, softness), dipole moment, electrostatic potential and thermodynamic properties (electronic energy, enthalpy, Gibb’s free energy) of these optimized drugs are investigated. Molecular docking has been performed against prostaglandin H2 (PGH2) synthase protein 5F19 to search the binding affinity and mode(s) of all compounds. It is found that, all compounds are thermodynamically stable; some of them are chemically more reactive and show better binding affinity than the parent drug. ADMET calculations predict the improved pharmacokinetic properties of all compounds. Finally, this study can be helpful for the design of new analgesic, antipyretic drug.

Understanding PPAR-δ affinity and selectivity using hologram quantitative structure–activity modeling, molecular docking and GRID calculations

2016 ◽  
Vol 8 (16) ◽  
pp. 1913-1926
Author(s):  
Vinicius G Maltarollo ◽  
Sheila C Araujo ◽  
Gustavo H G Trossini ◽  
Kathia M Honorio
Keyword(s):  
Molecular Docking ◽  
Quantitative Structure ◽  
Structure Activity ◽  
Activity Modeling

scholarly journals Vepris nobilis plant: a potential source of anticancer agents

2020 ◽  
Vol 8 (9) ◽  
pp. 3203
Author(s):  
Carolyne Chepkirui ◽  
Richard Kagia
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Topoisomerase I ◽  
Lethal Dose ◽  
Stem Bark ◽  
Docking Studies ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Online Tool ◽  
Potential Source

Background: Cancer is one of the major causes of death worldwide. Current cancer therapy is costly, it has poor therapeutic outcomes and many side effects. Therefore, new medications are needed. Plants have been used as sources of anticancer drugs. Vepris species have anticancer properties. The purpose of this study is to assess Vepris nobilis, a plant found in Kenya as a potential source of anticancer drugs.Methods: The dichloromethane/methanol (CH2Cl2/MeOH) 1:1 extract of the stem bark of Vepris nobilis led to the isolation of an alkaloid named, 4,6-dimethoxy-7-((3-methylbuta-1,3-dien-1-yl)oxy)furo[2,3-b]quinolone. SwissADME online tool was used to assess the compound’s pharmacokinetic parameters. Pass online tool identified potential targets while protox server described the toxicity of the compound. Chimera and Avogadro softwares were used for molecular docking studies.Results: In-silico pharmacokinetic studies, showed that the isolated compound complied with Lipinski rule of five, it showed high gastrointestinal activity, and it also inhibits cytochrome P450 (CYP) isoforms 1A2, 2C9 and 2C19. In toxicity studies the compound was relatively safe with a predicted median lethal dose (LD50) of 1600 mg/kg, apart from potential immunotoxicity and mutagenicity. Molecular docking studies demonstrated that, the compound has potential anticancer activity, it interacted with deoxyribonucleic acid (DNA) topoisomerase I in an almost similar manner to camptothecin though it had less binding potential.Conclusions: 4,6-dimethoxy-7-((3-methylbuta-1,3-dien-1-yl)oxy) furo[2,3-b]quinolone derived from Vepris nobilis is a potential drug for the management of cancer which can be administered orally.

scholarly journals Molecular docking and pharmacokinetic studies of phytocompounds from Nigerian Medicinal Plants as promising inhibitory agents against SARS-CoV-2 methyltransferase (nsp16)

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Tolulope Peter Saliu ◽  
Haruna I. Umar ◽  
Olawale Johnson Ogunsile ◽  
Micheal O. Okpara ◽  
Noriyuki Yanaka ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virus Detection ◽  
Docking Studies ◽  
Pharmacokinetic Studies ◽  
Docking Analysis ◽  
Viral Survival ◽  
Salvia Officinalis L ◽  
Inhibitory Agents

Abstract Background Since the index case was reported in China, COVID-19 has led to the death of at least 4 million people globally. Although there are some vaccine cocktails in circulation, the emergence of more virulent variants of SARS-CoV-2 may make the eradication of COVID-19 more difficult. Nsp16 is an S-adenosyl-L-Methionine-dependent methyltransferase that plays an important role in SARS-CoV-2 viral RNA cap formation—a crucial process that confers viral stability and prevents virus detection by cell innate immunity mechanisms. This unique property makes nsp16 a promising molecular target for COVID-19 drug design. Thus, this study aimed to identify potent phytocompounds that can effectively inhibit SARS-CoV-2 nsp16. We performed in silico pharmacokinetic screening and molecular docking studies using 100 phytocompounds—isolated from fourteen Nigerian plants—as ligands and nsp16 (PDB: 6YZ1) as the target. Results We found that only 59 phytocompounds passed the drug-likeness analysis test. However, after the docking analysis, only six phytocompounds (oxopowelline, andrographolide, deacetylbowdensine, 11, 12-dimethyl sageone, sageone, and quercetin) isolated from four Nigerian plants (Crinum jagus, Andrographis paniculata, Sage plants (Salvia officinalis L.), and Anacardium occidentale) showed good binding affinity with nsp16 at its active site with docking score ranging from − 7.9 to − 8.4 kcal/mol. Conclusions Our findings suggest that the six phytocompounds could serve as therapeutic agents to prevent viral survival and replication in cells. However, further studies on the in vitro and in vivo inhibitory activities of these 6 hit phytocompounds against SARS-CoV-2 nsp16 are needed to confirm their efficacy and dose.

scholarly journals Facing COVID-19 Via Anti-Inflammatory Mechanism of Action: Molecular Docking and Pharmacokinetic Studies of Six Anti-Inflammatory Compounds Derived from Passiflora edulis

2021 ◽  
pp. 35-51
Author(s):  
Aristote Matondo ◽  
Jason T. Kilembe ◽  
Domaine T. Mwanangombo ◽  
Beaudrique M. Nsimba ◽  
Dani T. Mawete ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Severe Case ◽  
Binding Energies ◽  
Inflammatory Activity ◽  
Pharmacokinetic Studies ◽  
Passiflora Edulis ◽  
Potential Inhibitor ◽  
Main Protease ◽  
Anti Inflammatory ◽  
Pharmacokinetic Behavior

Aim: In the most severe case of the COVID-19, there is an excessive production of proinflammatory cytokines, being the main cause of mortality and morbidity. The present study aims at assessing the potential inhibitor effect of six phytochemicals with anti-inflammatory activity derived from Passiflora edulis, against the SARS-CoV-2 main protease. Materials and Methods: Virtual screening by molecular docking (Autodock tool) was used to obtain the binding energies of ligand-protein complexes formed between each of the six ligands and the SARS-CoV-2 main protease. The six ligands were then submitted to ADME (absorption, distribution, metabolism and excretion) and toxicity analyses to understand their pharmacokinetic behavior, using SwissADME, preADMET and pkCSM webservers. Results: Four high-docking score compounds were identified (both flavonoids) as hits, with the trend: ligand 4 (quercetin, -8.2 kcal/mol ) > ligand 1 (chrysin, -8.0 kcal/mol) > ligand 2 (kaempferol, -7.9 kcal/mol) > ligand 3 (luteolin, -7.7 kcal/mol)> ligand 5 (harmol, -6.7 kcal/mol) > ligand 6 (harmine, -6.4 kcal/mol). The pharmacokinetic behavior of the six ligands revealed that they can be easily absorbed and have good permeability and bioavailability. The toxicity predictions of the six compounds from P. edulis which is an editable fruit confirm that they are safe. Conclusion: Several approaches are currently being used to tackle the COVID-19. Given the cytokine storm in the most severe case of the COVID-19, we adopted the strategy of combatting the disease by compounds that exhibit anti-inflammatory activity. The assessment of the efficiency of six phytochemicals from P. edulis against the SARS-CoV-2 Mpro and their pharmacokinetic profile revealed their potential inhibitor effect against the COVID-19 protein.

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