scholarly journals Molecular Modeling of Antimalarial Agents by 3D-QSAR Study and Molecular Docking of Two Hybrids 4-Aminoquinoline-1,3,5-triazine and 4-Aminoquinoline-oxalamide Derivatives with the Receptor Protein in Its Both Wild and Mutant Types

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Hanine Hadni ◽  
Mohamed Mazigh ◽  
El’mbarki Charif ◽  
Asmae Bouayad ◽  
Menana Elhallaoui
Keyword(s):  
Molecular Docking ◽  
3D Qsar ◽  
Qsar Model ◽  
Molecular Structures ◽  
Basis Set ◽  
Receptor Protein ◽  
Quantum Chemical Descriptors ◽  
Qsar Study ◽  
Antimalarial Agents ◽  
Quadruple Mutant

Modeling studies using 3D-QSAR and molecular docking methods were performed on a set of 34 hybrids of 4-aminoquinoline derivatives previously studied as effective antimalarial agents of wild type and quadruple mutant Plasmodium falciparum dihydrofolate reductase (DHFR). So, the famous mathematical method multiple linear regression (MLR) was explored to build the QSAR model. The DFT-B3LYP method with the basis set 6-31G was used to calculate the quantum chemical descriptors, chosen to represent the electronic descriptors of molecular structures. On the contrary, the MM2 method was used to calculate lipophilic, geometrical, physicochemical, and steric descriptors. The QSAR model tested with artificial neural network (ANN) method shows high performance towards its predictability. The predicted model was confirmed by three validation methods: leave-one-out (LOO) cross validation, Y-randomization, and validation external. The molecular docking study of three compounds 9, 11, and 26 on both wild and quadruple mutant types of pf-DHFR-TS as the protein target helps to understand more and then predict the binding modes with the binding sites.

scholarly journals STRUCTURAL EXPLORATION AND PHARMACOPHORIC INVESTIGATION OF PYRAZOLE BASED ANALOGS AS NOVEL HISTONE DEACETYLASE 1 INHIBITOR USING COMBINATORIAL STUDIES

2018 ◽  
Vol 10 (3) ◽  
pp. 90
Author(s):  
Avineesh Singh ◽  
Harish Rajak
Keyword(s):  
Molecular Docking ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Research Work ◽  
3D Qsar ◽  
Qsar Model ◽  
Docking Studies ◽  
Inhibition Activity ◽  
Design Strategies ◽  
Histone Deacetylase 1

Objective: Histone deacetylase inhibitors (HDACi) have four essential pharmacophores as cap group, connecting unit, a linker moiety and zinc binding group for their anticancer and histone deacetylase (HDAC) inhibition activity. On the basis of this fact, the objective of this research was to evaluate the exact role of pyrazole nucleus as connecting unit and its role in the development of newer HDACi.Methods: Ligand and structure-based computer-aided drug design strategies such as pharmacophore and atom based 3D QSAR modelling, molecular docking and energetic based pharmacophore mapping have been frequently applied to design newer analogs in a precise manner. Herein, we have applied these combinatorial approaches to develop the structure-activity correlation among novel pyrazole-based derivatives.Results: the Pharmacophore-based 3D-QSAR model was developed employing Phase module and e-pharmacophore on compound 1. This 3D-QSAR model provides fruitful information regarding favourable and unfavourable substitution on pyrazole-based analogs for HDAC1 inhibition activity. Molecular docking studies indicated that all the pyrazole derivatives bind with HDAC1 proteins and showed critical hydrophobic interaction with 5ICN and 4BKX HDAC1 proteins.Conclusion: The outcome of the present research work clearly indicated that pyrazole nucleus added an essential hydrophobic feature in cap group and could be employed to design the ligand molecules more accurately.

scholarly journals Combined 3D-QSAR and Molecular Docking Analysis of Thienopyrimidine Derivatives as Staphylococcus aureus Inhibitors

2021 ◽  
Vol 68 (2) ◽  
pp. 289-303
Author(s):  
Mebarka Ouassaf ◽  
Salah Belaidi ◽  
Saida Khamouli ◽  
Houmam Belaidi ◽  
Samir Chtita
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Docking ◽  
3D Qsar ◽  
Qsar Model ◽  
Structural Features ◽  
Positive Bacterium ◽  
Docking Analysis ◽  
Statistical Reliability ◽  
Starting Point ◽  
Effective Drugs

The discovery of antibacterials is considered one of the greatest medical achievements of all time. In this work, a combination of three computational analyzes: 3D-QSAR, molecular docking and ADME evaluation were applied in thienopyrimidine derivatives intended toward gram-positive bacterium Staphylococcus aureus. The validity of 3D-QSAR model was tested with a set of data which is divided into a training and a test set. The two models constructed (CoMFA and CoMSIA) show good statistical reliability (q2 = 0.758; r2 = 0.96; r2pred = 0.783) and (q2 = 0.744; r2 = 0.97; r2pred = 0.625) respectively. In addition, docking methods were applied to understand the structural features responsible for the affinity of the ligands in the binding of S. aureus DNA gyrase. Drug likeness and ADME analysis applied in this series of new proposed compounds, have shown that the five lead molecules would have the potential to be effective drugs and could be used as a starting point for designing compounds against Staphylococcus aureus.

MOLECULAR MODELING OF 5‐[(AMIDOBENZYL)OXY]‐ NICOTINAMIDES AS SIRTUIN 2 INHIBITORS USING ALIGNMENT- (IN)DEPENDENT 3D-QSAR ANALYSIS AND MOLECULAR DOCKING

2021 ◽  
Author(s):  
Nemanja Djokovic ◽  
◽  
Ana Postolovic ◽  
Katarina Nikolic
Keyword(s):  
Molecular Docking ◽  
Structural Similarity ◽  
3D Qsar ◽  
Quantitative Structure Activity Relationship ◽  
Study Data ◽  
Rational Drug Design ◽  
Qsar Study ◽  
Data Set ◽  
Qsar Analysis ◽  
Ligand Interactions

The group of 5‐[(amidobenzyl)oxy]‐nicotinamides represents promising group of sirtuin 2 (SIRT2) inhibitors. Despite structural similarity, representatives of this group of inhibitors displayed versatile mechanisms of inhibition which hamper rational drug design. The aim of this research was to form a 3D-QSAR (3D-Quantitative Structure-Activity Relationship) model, define the pharmacophore of this subgroup of SIRT2 inhibitors, define the mode of protein-ligand interactions and design new compounds with improved predicted activity and pharmacokinetics. For the 3D-QSAR study, data set was generated using structures and activities of 166 5‐[(amidobenzyl)oxy]‐nicotinamides. 3D-conformations of compounds were optimized, alignment-independent GRIND2 descriptors were calculated and 3D-QSAR PLS models were generated using 70% of data set. To investigate bioactive conformations of inhibitors, molecular docking was used. Molecular docking analysis identified two clusters of predicted bioactive conformations which is in alignment with experimental observations. The defined pharmacophoric features were used to design novel inhibitors with improved predicted potency and ADMET profiles.

A new, fully validated and interpreted quantitative structure-activity relationship model of p-aminosalicylic acid derivatives as neuraminidase inhibitors

2013 ◽  
Vol 67 (5) ◽  
Author(s):  
Ana Hartmman ◽  
Daniela Jornada ◽  
Eduardo Melo
Keyword(s):  
Predictive Ability ◽  
3D Qsar ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Neuraminidase Inhibitors ◽  
Aminosalicylic Acid ◽  
Randomization Tests ◽  
Qsar Study ◽  
Relationship Model ◽  
Mechanism Of Interaction

AbstractA multivariate QSAR study with a set of 34 p-aminosalicylic acid derivatives, described as neuraminidase inhibitors of the H1N1 viruses, is presented in this work. The variable selection was performed with the Ordered Predictors Selection (OPS) algorithm and the model was built with the Partial Least Squares (PLS) regression method. Leave-N-out cross-validation and y-randomization tests showed that the model was robust and free from chance correlation. The external predictive ability was superior to the 3D-QSAR model previously published. Moreover, it was possible to perform a mechanistic interpretation, where the descriptors referred directly to the mechanism of interaction with the neuraminidase.

scholarly journals Biological Activities Related to Plant Protection and Environmental Effects of Coumarin Derivatives: QSAR and Molecular Docking Studies

2021 ◽  
Vol 22 (14) ◽  
pp. 7283
Author(s):  
Vesna Rastija ◽  
Karolina Vrandečić ◽  
Jasenka Ćosić ◽  
Ivana Majić ◽  
Gabriella Kanižai Šarić ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Plant Protection ◽  
Biological Activities ◽  
Pathogenic Fungi ◽  
Qsar Model ◽  
Proteinase K ◽  
Coumarin Derivatives ◽  
Qsar Study ◽  
Pyrone Ring ◽  
Broth Microdilution Method

The aim was to study the inhibitory effects of coumarin derivatives on the plant pathogenic fungi, as well as beneficial bacteria and nematodes. The antifungal assay was performed on four cultures of phytopathogenic fungi by measuring the radial growth of the fungal colonies. Antibacterial activity was determined by the broth microdilution method performed on two beneficial soil organisms. Nematicidal activity was tested on two entomopathogenic nematodes. The quantitative structure-activity relationship (QSAR) model was generated by genetic algorithm, and toxicity was estimated by T.E.S.T. software. The mode of inhibition of enzymes related to the antifungal activity is elucidated by molecular docking. Coumarin derivatives were most effective against Macrophomina phaseolina and Sclerotinia sclerotiorum, but were not harmful against beneficial nematodes and bacteria. A predictive QSAR model was obtained for the activity against M. phaseolina (R2tr = 0.78; R2ext= 0.67; Q2loo = 0.67). A QSAR study showed that multiple electron-withdrawal groups, especially at position C-3, enhanced activities against M. phaseolina, while the hydrophobic benzoyl group at the pyrone ring, and –Br, –OH, -OCH3, at the benzene ring, may increase inhibition of S. sclerotiourum. Tested compounds possibly act inhibitory against plant wall-degrading enzymes, proteinase K. Coumarin derivatives are the potentially active ingredient of environmentally friendly plant-protection products.

scholarly journals Synthesis, 3D-QSAR and Molecular Docking Study of Nopol-Based 1,2,4-Triazole-Thioether Compounds as Potential Antifungal Agents

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiu Wang ◽  
Wengui Duan ◽  
Guishan Lin ◽  
Baoyu Li ◽  
Ming Chen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antifungal Activity ◽  
Plant Pathogens ◽  
3D Qsar ◽  
Docking Study ◽  
Qsar Model ◽  
Molecular Docking Study ◽  
Activity Data ◽  
Target Enzyme

Cytochrome bc1 complex is an important component of cellular respiratory chain, and it is also an important target enzyme to inhibit the growth of plant pathogens. Using cytochrome bc1 complex as the target enzyme, twenty-three novel nopol-based 1,2,4-triazole-thioether compounds were designed and synthesized from natural preponderant resource β-pinene, and their structures were confirmed by FT-IR, NMR, ESI-MS and elemental analysis. The in vitro antifungal activity of the target compounds 5a-5w was preliminarily evaluated against eight plant pathogens at the concentration of 50 µg/ml. The bioassay results showed that the target compounds exhibited the best antifungal activity against Physalospora piricola, in which compounds 5b (R= o-CH3 Ph), 5e (R= o-OCH3 Ph), 5h (R= o-F Ph), 5m (R= o-Br Ph), 5o (R= m,m-OCH3 Ph), and 5r (R= p-OH Ph) had inhibition rates of 91.4, 83.3, 86.7, 83.8, 91.4 and 87.3%, respectively, much better than that of the positive control chlorothalonil. Also, compound 5a (R= Ph) had inhibition rate of 87.9% against Rhizoeotnia solani, and compound 5b (R= o-CH3 Ph) had inhibition rates of 87.6 and 89% against Bipolaris maydis and Colleterichum orbicala, respectively. In order to develop novel and promising antifungal compounds against P. piricola, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method on the basis of their antifungal activity data, and a reasonable and effective 3D-QSAR model (r2 = 0.944, q2 = 0.685) has been established. In addition, the theoretical study of molecular docking revealed that the target compounds could bind to and interact with the site of cytochrome bc1 complex.

A QSAR study of peptidyl vinyl sulfone cysteine protease inhibitors using Topomer CoMFA and Molecular Docking

2021 ◽  
Vol 18 ◽  
Author(s):  
WU Lu-Yang ◽  
MA Yang-Min ◽  
LEI Shan ◽  
WANG Tian-Hao ◽  
FENG Yi
Keyword(s):  
Molecular Docking ◽  
Protease Inhibitors ◽  
Cysteine Protease ◽  
Active Site ◽  
3D Qsar ◽  
Vinyl Sulfone ◽  
Cysteine Protease Inhibitors ◽  
Qsar Study ◽  
Topomer Comfa ◽  
Topomer Search

Background: Malaria is one of the most important infectious diseases in the world. The most severe form of malaria in humans is caused by Plasmodium falciparum. Malaria is a worldwide health problem, with 214 million new cases in 2015 and 438,000 deaths, most of which in Africa. Therefore, there is an urgent need for novel, low-toxic, more specific inhibitors to find new antimalarial agents. A promising target for antimalarial drug design is falcipain-2, a cysteine protease from P. falciparum, that has received considerable attention due to its key role in the life cycle of the parasite. Methods: Three-dimensional quantitative structure-activity relationship (3D-QSAR) models of 39 peptidyl vinyl sulfone cysteine protease inhibitors was constructed using Topomer CoMFA. Topomer Search was employed to virtually screen lead-like compounds in the ZINC database. Molecular docking was employed to further explore the binding requirements between the ligands and the receptor protein which included several hydrogen bonds between peptidyl vinyl sulfone cysteine protease inhibitors and active site residues. Results: The non-cross correlation coefficient (r 2 ), the interaction validation coefficient (q2 ) and the external validation (r 2 pred) were 0.902, 0.685 and 0.763, respectively. The results showed that the model not only had good estimation stability but also good prediction capability. 22 new molecules were obtained, whose predicted activity are higher than template molecules. The results showed that the Topomer Search technology can be effectively applied to screen and design new peptidyl vinyl sulfone cysteine protease inhibitors. Molecular docking showed extensive interactions between peptidyl vinyl sulfone cysteine protease inhibitors and residues of LYS24, ASP21, LYS59 and ASP17 in the active site. Conclusion: 39 peptidyl vinyl sulfone cysteine protease inhibitors were used in the 3D-QSAR study. Topomer CoMFA 3DQSAR method was used to build the model, and the model was well predicted and statistically validated. The design of potent new inhibitors of cysteine protease can get useful insights from these results.

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