Structural Requirements for some 3-amino-N-substituted-4-(substituted phenyl) Butanamides as Dipeptidyl Peptidase-IV Inhibitors Using 3D-QSAR and Molecular Docking Approaches

Ghode, Piyush; Jain, Sanmati K.

doi:10.4172/pharmaceutical-sciences.1000315

Cited by 5 publications

(1 citation statement)

References 24 publications

(29 reference statements)

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“…The docking programs like AutoDock, AutoDock Vina, FlexX, DOCK, Surflex, GOLD, Glide, ICM, Cdcker, LigandFit, FRED, MCDock, MOE-Dock, LeDock, rDock and UCSF Dock are used. Among this software AutoDock vina, Glide and GOLD are the top-ranking choices with the best scores [12][13][14] . GOLD and LeDock are commonly preferred to identify the correct ligand binding site [15,16] .…”

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confidence: 99%

Review on the use of Molecular Docking as the First Line Tool in Drug Discovery and Development

Sahoo¹,

Pattanaik²,

Pattnaik³

et al. 2022

IJPS

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Sahoo et al.: Molecular Docking and Drug DevelopmentMolecular docking has now become a novel approach for drug discovery in recent years. Computer-aided drug design is an area that is rapidly growing and has seen many successes. Many big pharmaceutical industries, academic resources and research personnel are using the tools for new drug development. In this review, we have discussed briefly different molecular docking methods, software used in the molecular docking process and their application in drug discovery. Molecular docking is a configuration-based virtual tryout in which computer-generated three dimensional structures of small molecules are given the freedom to interact with the target structure in assorted positions, orientation, and conformations.

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confidence: 99%

Review on the use of Molecular Docking as the First Line Tool in Drug Discovery and Development

Sahoo¹,

Pattanaik²,

Pattnaik³

et al. 2022

IJPS

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Molecular Docking and Computational In Silico Investigations of Metal-Based Drug Agents

Arjmand,

Tabassum,

Khan

2024

Advances and Prospects of 3-D Metal-Based Anticancer Drug Candidates

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In silico exploration of antinociceptive activity of 1,4-benzodiazepines: Molecular docking on α1 A-adrenoceptor, and phosphodiesterase 4

Akisheva,

Larionov,

Golovenko

et al. 2024

Regul. Mech. Biosyst.

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Recently, scientists have established that several benzodiazepines were found to enhance the activation of a cAMP response element pathway by α1A-adrenergic receptors, but this effect was attributed to off-target inhibition of phosphodiesterases 4. The study explores the pain-relief potential of 1,4-benzodiazepines using in silico methods, focusing on their interaction with α1A-adrenoceptors (α1-AR) and phosphodiesterase 4 (PDE4). AutoDock Vina-1.2.5 and Glide (Schrödinger Suite) (2023-2) were used to calculate the binding affinities and determine the features of their interactions by the molecular docking method; PlayMolecule software was used to perform molecular dynamics. Propoxazepam exhibits moderate free binding energy for α1A-adrenoceptors, as indicated by its average molecular mechanics/generalized Born surface area (MMGBSA) and Glide Score values. Compared to propoxazepam, 3-hydroxypropoxazepam has enhanced predicted affinity values for the alpha 1A adrenergic receptor, primarily due to the hydroxyl group, which facilitates the formation of additional hydrogen bonds. Propoxazepam, along with its metabolite 3-hydroxypropoxazepam, demonstrates promising interactions with PDE4A, characterized by notably low predicted free binding energy MMGBSA and strong binding affinity computed via AutoDock Vina. Among other ligands, propoxazepam demonstrates the lowest MMGBSA value with PDE4A (phosphodiesterase 4A). The best predicted binding scores of interaction with phosphodiesterase 4 is observed for propoxazepam with PDE4B (phosphodiesterase 4B) -10.3 kcal/mol, according to AutoDock Vina. Propoxazepam and its derivative 3-hydroxypropoxazepam interact with the active sites of PDE4B and PDE4D (phosphodiesterase 4 B) via a “hydrophobic clamp”, a typical binding mode for PDE inhibitors, which relies on crucial hydrophobic interactions. Binding of propoxazepam and its metabolite 3-hydroxypropoxazepa to PDE4B reduces the fluctuations of M-pocket residues and supports the conclusion that ligand binding stabilizes the protein structure of PDE4B. The MMGBSA method predicts that propoxazepam and 3-hydroxypropoxazepam have the most favourable predicted binding energies with PDE4D (2FMO). Since 1,4-benzodiazepines bind to phosphodiesterase 4 similarly to its inhibitors, this may support the hypothesis that benzodiazepines may affect α1-AR by inhibiting PDE4. The study of the binding mechanisms of 1,4-benzodiazepines with phosphodiesterase 4 and alpha-1A adrenoceptors helps to expand the understanding of the analgesic and anti-inflammatory effect of benzodiazepines associated with these proteins, which can be taken into account in the development of new analgesic and anti-inflammatory agents.

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Structural Requirements for some 3-amino-N-substituted-4-(substituted phenyl) Butanamides as Dipeptidyl Peptidase-IV Inhibitors Using 3D-QSAR and Molecular Docking Approaches

Cited by 5 publications

References 24 publications

Review on the use of Molecular Docking as the First Line Tool in Drug Discovery and Development

Review on the use of Molecular Docking as the First Line Tool in Drug Discovery and Development

Molecular Docking and Computational In Silico Investigations of Metal-Based Drug Agents

In silico exploration of antinociceptive activity of 1,4-benzodiazepines: Molecular docking on α1 A-adrenoceptor, and phosphodiesterase 4

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