Molecular docking study of A3 adenosine receptor antagonists and pharmacophore-based drug design

The synthesis, crystal structure and spectroscopic and electronic properties of N-(2-methyl-5-nitrophenyl)-4-(pyridin-2-yl)pyrimidin-2-amine (NPPA), C16H13N5O2, a potential template for drug design against chronic myelogenous leukemia (CML), is reported. The design and construction of the target molecule were carried out starting from the guanidinium nitrate salt (previously synthesized) and the corresponding enaminone. X-ray diffraction analysis and a study of the Hirshfeld surfaces revealed important interactions between the nitro-group O atoms and the H atoms of the pyridine and pyrimidine rings. A crystalline ordering in layers, by the stacking of rings through interactions of the π–π type, was observed and confirmed by a study of the shape-index surfaces and dispersion energy calculations. Quantitative electrostatic potential studies revealed the most positive value of the molecule on regions close to the N—H groups (34.8 kcal mol−1); nevertheless, steric impediments and the planarity of the molecule do not allow the formation of hydrogen bonds from this group. This interaction is however activated when the molecule takes on a new extended conformation in the active pocket of the enzyme kinase (PDB ID 2hyy), interacting with protein residues that are fundamental in the inhibition process of CML. The most negative values of the molecule are seen in regions close to the nitro group (−35.4 and −34.0 kcal mol−1). A molecular docking study revealed an energy affinity of ΔG = −10.3 kcal mol−1 for NPPA which, despite not having a more negative value than the control molecule (Imatinib; ΔG = −12.8 kcal mol−1), shows great potential to be used as a template for new drugs against CML.

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Isolation of tetramer stilbenoids from Shorea leprosula Miq., acetylcholinesterase inhibitory activity and molecular docking study

10.1055/s-0039-3399897 ◽

2019 ◽

Author(s):

AS Kamarozaman ◽

N Ahmat ◽

MSM Johari ◽

ZZ Hafiz ◽

MI Adenan ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Docking Study ◽

Molecular Docking Study ◽

Acetylcholinesterase Inhibitory Activity ◽

Shorea Leprosula

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

10.3390/ecsoc-19-e012 ◽

2015 ◽

Author(s):

Manik Ghosh ◽

Kamal Kant ◽

Anoop Kumar ◽

Padma Behera ◽

Naresh Rangra ◽

...

Keyword(s):

Molecular Docking ◽

In Silico ◽

Docking Study ◽

Molecular Docking Study

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

10.26434/chemrxiv.12362996 ◽

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>

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Design, synthesis, anti-inflammatory assessment and molecular docking study of novel ketorolac analogues as potent anti-inflammatory agents targeting cyclooxygenase-2 enzyme

10.36295/asro.2020.232129 ◽

2020 ◽

Vol 23 (19) ◽

Author(s):

Farah AH. Kadhim ◽

Noor M. Mohammed ◽

Haider M. Badea Albadr

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Cyclooxygenase 2 ◽

Molecular Docking Study ◽

Design Synthesis ◽

Anti Inflammatory

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

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021999201110204116 ◽

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.

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