Molecular modeling of histamine H3 receptor and QSAR studies on arylbenzofuran derived H3 antagonists

Dastmalchi, Siavoush; Hamzeh‐Mivehroud, Maryam; Ghafourian, Taravat; Hamzeiy, Hossein

doi:10.1016/j.jmgm.2007.05.002

Cited by 37 publications

(22 citation statements)

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“…Another bovine rhodopsin based H3R model was used to rationalize the binding modes of arylbenzofurans [30]. The initial model was built by Swiss-Model server and subsequently short MD simulation in a water-vacuum-water environment was applied.…”

Section: H3 Receptormentioning

confidence: 99%

Structure-based discovery and binding site analysis of histamine receptor ligands

Kingsford-Adaboh

Keserü

2016

Expert Opinion on Drug Discovery

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Introduction: Application of structure-based drug discovery in histamine receptor projects was previously hampered by the lack of experimental structures. The publication of the first X-ray structure of the histamine H1 receptor has been followed by several successful virtual screens and binding site analysis studies of H1-antihistamines. This structure together with several other recently solved aminergic G-protein coupled receptors (GPCRs) enabled the development of more realistic homology models for H2, H3 and H4 receptors. Areas covered: In this paper, we review the development of histamine receptors models and their application on drug discovery. Expert opinion: In our opinion, the application of atomistic histamine receptor models played a significant role in understanding key ligand-receptor interactions as well as in the discovery of novel chemical starting points. The recently solved H1 receptor structure is a major milestone in structure-based drug discovery, however our analysis also demonstrate that for building H3 and H4 receptor homology models other GPCRs may be more suitable as a template. For these receptors we envisage that the development of higher quality homology models will significantly contribute to the discovery and optimization of novel H3 and H4 ligands.

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Section: H3 Receptormentioning

confidence: 99%

Structure-based discovery and binding site analysis of histamine receptor ligands

Kingsford-Adaboh

Keserü

2016

Expert Opinion on Drug Discovery

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“…In another study, ∼ 58 arylbenzofurane derivatives acting as H 3 R antagonists were analyzed by QSAR [67]. Several descriptors, like HOMO and LUMO energies, molar refractivity, hydration energy, logP, dipole moment, surface area, total energy, molar volume, surface tension and others were calculated.…”

Section: The Histamine H 3 Receptor and Its Ligandsmentioning

confidence: 99%

Molecular modeling and QSAR-based design of histamine receptor ligands

Straßer

2009

Expert Opinion on Drug Discovery

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There have been several new studies in the past years aimed at developing new histamine receptor ligands on the one hand and at explaining pharmacological profiles on molecular level on the other. For these purposes, not only molecular modeling techniques, but also synthesis, pharmacological characterization, molecular biological and physical techniques are useful. This combination of several different theoretical and experimental techniques allows getting a more detailed insight into the interaction of histamine receptor ligands with histamine receptors and developing new drugs.

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“…[14] Several 3D-QSAR studies with regard to the histamine H 1 R, H 2 R and H 3 R were performed. [15][16][17][18][19][20] In case of hH 1 R and gpH 1 R, a temperature-dependent 3D-QSAR-CoMFA study was performed, to predict binding enthalpy and binding entropy for H 1 R agonists. [21] We used the 3D-QSAR CoMFA technique to predict pK i values on the one hand and to calculate the percentage of suprahistaprodifens and phenoprodifens, bound in orientation 1 or 2 in the binding-pocket of hH 1 R, rH 1 R, bH 1 R and gpH 1 R on the other hand.…”

Section: Introductionmentioning

confidence: 99%

3D‐QSAR CoMFA Study to Predict Orientation of Suprahistaprodifens and Phenoprodifens in the Binding‐Pocket of Four Histamine H₁‐Receptor Species

Straßer

Wittmann

2010

Molecular Informatics

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Several phenylhistamines and histaprodifens were identified to act as (partial) agonists at the histamine H1 -receptor (H1 R). The large diversity of these compounds led to pKi values in a range between 4.5-7.5 at human, rat, bovine and guinea-pig histamine H1 R. Hybrid molecules, consisting of two different H1 R-agonist partial structures, like suprahistaprodifens or phenoprodifens for example, or compounds with a dimeric histamine moiety are able to bind in two different orientations into the binding-pocket of the H1 R. In order to predict the percentage of ligand bound in orientation 1 or in orientation 2, 3D-QSAR studies at four H1 R species were performed. The training set contains ligands which can only bind in one orientation and the test set all ligands with two possible orientations. In general, the predicted pKi values of the test compounds were in good correlation to the experimental ones. Additionally, the predicted pKi values for all ligands with two possible orientations were used to calculate the percentage of the hybrid ligands bound in orientation 1 and 2. Our models suggest that the preferred orientation of these hybrid molecules is dependent on ligand and H1 R species.

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Molecular modeling of histamine H3 receptor and QSAR studies on arylbenzofuran derived H3 antagonists

Cited by 37 publications

References 50 publications

Structure-based discovery and binding site analysis of histamine receptor ligands

Structure-based discovery and binding site analysis of histamine receptor ligands

Molecular modeling and QSAR-based design of histamine receptor ligands

3D‐QSAR CoMFA Study to Predict Orientation of Suprahistaprodifens and Phenoprodifens in the Binding‐Pocket of Four Histamine H₁‐Receptor Species

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Molecular modeling of histamine H3 receptor and QSAR studies on arylbenzofuran derived H3 antagonists

Cited by 37 publications

References 50 publications

Structure-based discovery and binding site analysis of histamine receptor ligands

Structure-based discovery and binding site analysis of histamine receptor ligands

Molecular modeling and QSAR-based design of histamine receptor ligands

3D‐QSAR CoMFA Study to Predict Orientation of Suprahistaprodifens and Phenoprodifens in the Binding‐Pocket of Four Histamine H1‐Receptor Species

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3D‐QSAR CoMFA Study to Predict Orientation of Suprahistaprodifens and Phenoprodifens in the Binding‐Pocket of Four Histamine H₁‐Receptor Species