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.

scholarly journals 3D-QSAR and molecular docking analysis of (4-piperidinyl)-piperazines as acetyl-CoA carboxylases inhibitors

2017 ◽  
Vol 10 ◽  
pp. S617-S626 ◽  
Author(s):  
Udghosh Singh ◽  
Rahul Prakashchand Gangwal ◽  
Gaurao V. Dhoke ◽  
Rameshwar Prajapati ◽  
Mangesh Damre ◽  
...  
Keyword(s):  
Molecular Docking ◽  
3D Qsar ◽  
Acetyl Coa ◽  
Docking Analysis ◽  
Molecular Docking Analysis

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 Construction of immunoglobulin-binding peptides based on analysis of the protein A of Staphylococcus aureus interaction with immunoglobulins Fc fragment

2019 ◽  
Vol 55 (4) ◽  
pp. 447-454
Author(s):  
A. V. Lapko ◽  
E. S. Pustyul’ga ◽  
V. P. Golubovich
Keyword(s):  
Staphylococcus Aureus ◽  
Molecular Docking ◽  
Amino Acid ◽  
Protein A ◽  
New Drugs ◽  
Amino Acid Residues ◽  
Fc Fragment ◽  
Peptide Analog ◽  
Identify Amino Acid ◽  
Starting Point

Over the past decades, molecular docking has become an increasingly popular tool for the development of new drugs. To search and design new compounds, a detailed study of the interaction of existing complexes of ligands with the target protein is necessary. According to the purpose to identify amino acid residues of the B domain of protein A of Staphylococcus aureus involved in interaction with immunoglobulins G, we studied the interaction mechanisms during the formation of a complex of protein A of the Staphylococcus aureus cell wall and immunoglobulins G by molecular docking. By the means of molecular docking we selected four amino acid residues of Phe132, Gln129, Tyr133 and Phe124, which we can use to construct a peptide analog of the active binding site of protein A with the Fc fragment of immunoglobulins G. The obtained results can serve as starting point for an effective strategy for finding new medicines, in particular, they can be used to further develop biospecific sorbent for the selective removal of immunoglobulins G from human blood.

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