scholarly journals Comprehensive Modeling and Molecular Docking of Phosphodiesterase Inhibitors

2021 ◽  
Author(s):  
zahra khosravi ◽  
elham baher ◽  
sajad gharaghani ◽  
salma ehsani
Keyword(s):  
Molecular Docking ◽  
Linear Models ◽  
Phosphodiesterase Inhibitors ◽  
Docking Study ◽  
Projection Algorithm ◽  
Support Vector ◽  
Molecular Docking Study ◽  
Qsar Study ◽  
Qsar Studies ◽  
Non Linear

Abstract In the present study, the biological activity of some pharmaceutical molecules was investigated and predicted by using quantitative structure-activity relationship (QSAR) studies and molecular docking. The aim of this study is to apply QSAR and molecular docking methods to predict and calculate the half maximal inhibitory concentration (IC50) of phosphodiesterase (PDE) 10A. To apply QSAR method at first multiple linear regression (MLR), genetic algorithm (GA), and successive projection algorithm (SPA) were used to select the best descriptors related to PDE 10A inhibitory activity. The selected descriptors were then applied as inputs to construct MLR and a non-linear support vector machine (SVM). Also we used molecular docking method to extract the descriptors and then by using MLR and SVM methods a linear and non-linear models developed respectively. Consequently, a comparison of the results of QSAR and docking study indicated that the non-linear SVM-SPA2 in QSAR study and SVM-MLR in molecular docking study had a much better prediction power than the other models. Finally, the Y-scrambling and cross-validation tests were used to evaluate the validity of the obtained model and the results of these tests indicates that the model is appropriate for using in prediction.

scholarly journals Molecular Docking and QSAR Study of Chalcone and Pyrimidine Derivatives as Potent Anti-Malarial Agents against Plasmodium falciparum

2020 ◽  
Vol 85 ◽  
pp. 23-34
Author(s):  
Dayena J. Christian ◽  
Rajesh H. Vekariya ◽  
Kinjal D. Patel ◽  
Dhanji P. Rajani ◽  
Smita D. Rajani ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Antimalarial Activity ◽  
Docking Study ◽  
Quantitative Structure Activity Relationship ◽  
Negative Influence ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Study ◽  
Qsar Study ◽  
Data Set

A data set of chalcone and pyrimidine derivatives with anti-malarial activity against Plasmodium falciparum was employed in investigating the quantitative structure-activity relationship (QSAR). Molecular docking study was performed for plasmodium falciparum dihydrofolate reductase (PfDHFR-TS). Genetic function approximation (GFA) technique was used to identify the descriptors that have influence on anti-malarial activity. The most influencing molecular descriptors identified include thermodynamics, structural and physical descriptors. Generated model was found to be good based on correlation coefficient, LOF, rm2 and rcv2 values. Nrotb, solubility, polarizibility may have negative influence on antimalarial activity or play an important role in growth inhibition of Plasmodium falciparum. The QSAR models so constructed provide fruitful insights for the future development of anti-malarial agents.

EVALUATION OF IN-SILICO ANTICANCER POTENTIAL OF PYRETHROIDS: A COMPARATIVE MOLECULAR DOCKING STUDY

2015 ◽  
Author(s):  
Manik Ghosh ◽  
Kamal Kant ◽  
Anoop Kumar ◽  
Padma Behera ◽  
Naresh Rangra ◽  
...  
Keyword(s):  
Molecular Docking ◽  
In Silico ◽  
Docking Study ◽  
Molecular Docking Study

Myricetin Preferentially Binds to Interfacial Regions in Domains 1 – 3 to Inhibit Cholesterol-Dependent Cytolysins: A Molecular Docking Study

2020 ◽  
Author(s):  
Rafael Espiritu
Keyword(s):  
Molecular Docking ◽  
Structural Changes ◽  
Docking Study ◽  
Listeriolysin O ◽  
Molecular Docking Study ◽  
Docking Analysis ◽  
Streptolysin O ◽  
Molecule Inhibitor ◽  
Human Cd59 ◽  
Anthrolysin O

<p>Cholesterol-dependent cytolysins (CDCs) are proteinaceous toxins secreted as monomers by some Gram-positive and Gram-negative bacteria that contribute to their pathogenicity. These toxins bind to either cholesterol or human CD59, leading to massive structural changes, toxin oligomerization, formation of very large pores, and ultimately cell death, making these proteins promising targets for inhibition. Myricetin, and its related flavonoids, have been previously identified as a candidate small molecule inhibitor of specific CDCs such as listeriolysin O (LLO) and suilysin (SLY), interfering with their oligomerization. In this work, molecular docking was performed to assess the interaction of myricetin with other CDCs whose crystal structures are already known. Results indicated that although myricetin bound to the hitherto identified cavity in domain 4 (D4), much more efficient and stable binding was obtained in sites along the interfacial regions of domains 1 – 3 (D1 – D3). This was common among the tested CDCs, which was primarily due to much more extensive stabilizing intermolecular interactions, as indicated by post-docking analysis. Specifically, myricetin bound to (1) the interface of the three domains in anthrolysin O (ALO), perfringolysin O (PFO), pneumolysin (PLY), SLY, and vaginolysin (VLY), (2) at/near the D1/D3 interface in LLO and streptolysin O (SLO), and (3) along the D2/D3 interface in intermedilysin (ILY). These findings provide theoretical basis on the possibility of using myricetin and its related compounds as a broad-spectrum inhibitor of CDCs to potentially address the diseases associated with these pathogens.</p>

Computational Evidences of Phytochemical Mediated Disruption of PLpro Driven Replication of SARS-CoV-2: A Therapeutic Approach Against COVID-19

2020 ◽  
Vol 21 ◽  
Author(s):  
Acharya Balkrishna ◽  
Rashmi Mittal ◽  
Vedpriya Arya
Keyword(s):  
Molecular Docking ◽  
Md Simulation ◽  
Bond Distance ◽  
Immunological Response ◽  
Docking Study ◽  
Receptor Interaction ◽  
Molecular Docking Study ◽  
Replication Process ◽  
Stable Conformation ◽  
Distance Analysis

Background:: COVID-19 caused by SARS-CoV-2 has been declared as global pandemic by WHO. Comprehensive analysis of this unprecedented outbreak may help to fight against the disease and may play a pivotal role in decreasing the mortality rate linked with it. Papain like protease (PLpro), a multifunctional polyprotein facilitates the replication of SARS-CoV-2 and evades it from the host immunological response by antagonizing cytokines, interferons and may be considered as potential drug target to combat the current pandemic. Methods:: Natural moieties obtained from medicinal plants were analysed for their potency to target PLpro of SARS-CoV-2 by molecular docking study and were compared with synthetic analogs named as remdesivir, chloroquine and favipiravir. The stability of complexes of top hits was analysed by MD Simulation and interaction energy was calculated. Furthermore, average RMSD values were computed and deepsite ligand binding pockets were predicted using Play Molecule. Drug like abilities of these moieties were determined using ADMET and bond distance between the ligand and active site was assessed to predict the strength of interaction. Results:: Nimbocinol (-7.6 Kcal/mol) and sage (-7.3 Kcal/mol) exhibited maximum BA against PLpro SARS-CoV-2 as evident from molecular docking study which was found to be even better than remdesivir (-6.1 Kcal/mol), chloroquine (-5.3 Kcal/mol) and favipiravir (-5.7 Kcal/mol). Both nimbocinol-PLpro and sage-PLpro SARS-CoV-2 complex exhibited stable conformation during MD Simulation of 101ns at 310 K and potential, kinetic and electrostatic interaction energies were computed which was observed to be concordant with results of molecular docking study. RMSD average values were found to be 0.496 ± 0.015 Å and 0.598 ± 0.023 Å for nimbocinol and sage respectively thus revealing that both the deviation and fluctuations during MD Simulation were observed to be least. Deepsite prediction disclosed that both compounds occupied cryptic pockets in receptor and non-bond distance analysis revealed the formation of hydrogen bonds during ligand-receptor interaction. ADMET exploration further validated the drug like properties of these compounds. Conclusion:: Present study revealed that active constituents of Azadirachta indica and Salvia officinalis can be potentially used to target SARS-CoV-2 by hindering its replication process.

Design, Synthesis, Antimicrobial and Anti-biofilm Evaluation, and Molecular Docking of Newly Substituted Fluoroquinazolinones

2019 ◽  
Vol 15 (6) ◽  
pp. 659-675
Author(s):  
Mohamed F. Zayed ◽  
Sabrin R.M. Ibrahim ◽  
EL-Sayed E. Habib ◽  
Memy H. Hassan ◽  
Sahar Ahmed ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Receptor Site ◽  
Docking Study ◽  
Diffusion Method ◽  
Molecular Docking Study ◽  
Active Compounds ◽  
Highly Active ◽  
Strong Binding ◽  
Agar Disc

Background: Quinazolines and quinazolinones derivatives are well known for their important range of therapeutic activities. Objective: The study aims to carry out the synthesis of some derivatives of substituted fluoroquinazolinones based on structure-based design and evaluation of their antibacterial, antifungal, and anti-biofilm activities. Methods: Compounds were chemically synthesized by conventional methods. Structures were established on the basis of spectral and elemental analyses. The antimicrobial potential was tested against various microorganisms using the agar disc-diffusion method. MIC and MBC as well as anti-biofilm activity for the highly active compounds were assessed. Moreover, the computational studies were performed using Auto dock free software package (version 4.0) to explain the predicted mode of binding. Results: All derivatives (5-8), (10a-g), and (A-H) were biologically tested and showed significant antimicrobial activity comparable to the reference compounds. Compounds 10b, 10c, and 10d had a good MIC and MBC against Gram-positive bacteria, whereas 10b and 10d showed significant MIC and MBC against Gram-negative bacteria. However, compounds E and F exhibited good MIC and MBC against fungi. Compound 10c and 8 exhibited significant anti-biofilm activity towards S. aureus and M. luteus. Molecular docking study revealed a strong binding of these derivatives with their receptor-site and detected their predicted mode of binding. Conclusion: The synthesized derivatives showed promising antibacterial, antifungal, and antibiofilm activities. Modeling study explained their binding mode and showed strong binding affinity with their receptor-site. The highly active compounds 5 and 10c could be subjected to future optimization and investigation to be effective antimicrobial agents.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

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