Structural analysis of (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol and binding mechanism with α1A-adrenoceptor: TDDFT calculations, X-ray crystallography and molecular docking

Xü, Wei; Shao, Binhao; Xu, Xiaojie; Jiang, Ren‐Wang; Yuan, Ming

doi:10.1016/j.molstruc.2015.10.031

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…The docking procedures were performed in AutoDock Vina using the default scorning function 15 . The binding site was identified according to previous studies 16 . Exhaustiveness was set to 100, and number of output conformations was set to 20.…”

Section: Methodsmentioning

confidence: 99%

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as α 1D -adrenoceptor antagonists

Xü

Huang

Jiang

et al. 2017

Acta Pharmaceutica Sinica B

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Chiral drug naftopidil (NAF), a specific α1D-adrenoceptor (AR) antagonist for the treatment of benign prostatic hyperplasia, was used in racemic form for several decades. Our recent work declared that NAF enantiomers showed the same antagonistic effects on the α1D-AR, but the binding mechanism of these two stereochemical NAF isomers to the α1D receptor remained unclear. Herein, we reported the crystallographic structures of optically pure NAF stereoisomers for the first time and unambiguously determined their absolute configurations. The crystal data of R and S enantiomers matched satisfactorily the pharmacophore model for α1D-selective antagonists. Based on the constructed α1D homology model, molecular docking studies shed light on the molecular mechanism of NAF enantiomers binding to α1D-AR. The results indicated that NAF enantiomers exhibited the very similar binding poses and occupied the same binding pocket.

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Section: Methodsmentioning

confidence: 99%

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as α 1D -adrenoceptor antagonists

Xü

Huang

Jiang

et al. 2017

Acta Pharmaceutica Sinica B

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“…Drug–protein interaction analysis is central in clarifying protein functions, explaining drug action mechanisms and uncovering novel drug candidates (Guo, Heitman, & Ijzerman, ; Kumari, Eshan, & Arun, ; Hansen et al, ). A number of techniques have been successfully utilized to examine drug–protein interactions, including equilibrium dialysis‐related technology (Abbas, Ahmad, Shah, Gill, & Watson, ), capillary electrophoresis (Bao et al, ), ultraviolet–visible absorption spectrometry (Szczepek et al, ), X‐ray crystal diffraction (Xu, Shao, Xu, Jiang, & Yuan, ), circular dichroism (Fabini, Fiori, Tedesco, Lopes, & Bertucci, ), fluorescent spectrometry (Arroyo‐Maya, Campos‐Terán, Hernández‐Arana, & McClements, ; Li, Duan, et al, ), micro calorimetry (Abdallah, ), surface plasmon resonance (Simon, ; Stigter, Jong, & Bennekom, ), nuclear magnetic resonance (Wu et al, ) and chromatographic methods (Bi, Zheng, & Hage, ; Zheng, Bi, Brooks, & Hage, ; Zheng, Li, Podariu, & Hage, ). These approaches, however, have limitations of long performance times, requirements of protein with high concentration or purity, potential interfering substances from the sample and a need for relatively specialized equipment, especially in quantitative determination of drug–protein interactions where measurement of association constants, association and dissociation rate constants is routinely needed.…”

Section: Introductionmentioning

confidence: 99%

Rapid analysis of interaction between six drugs and β₂‐adrenergic receptor by injection amount‐dependent method

Zeng

Wang

Sun

et al. 2017

Biomedical Chromatography

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Drug-protein interaction analysis has become a considerable topic in life science which includes clarifying protein functions, explaining drug action mechanisms and uncovering novel drug candidates. This work was to determine the association constants (K ) of six drugs to β -adrenergic receptor by injection amount-dependent method using stationary phase containing the immobilized receptor. The values of K were calculated to be (25.85 ± 0.035) × 10 m for clorprenaline, (42.51 ± 0.054) × 10 m for clenbuterol, (6.67 ± 0.008) × 10 m for terbutaline, (33.99 ± 0.025) × 10 m for tulobuterol, (7.59 ± 0.011) × 10 m for salbutamol and (78.52 ± 0.087) × 10 m for bambuterol. This rank order agreed well with the data determined by zonal elution, frontal analysis and nonlinear chromatography, even using different batches of β -AR column. A good correlation was found between the association constants by the current method and radio-ligand binding assay. Our data indicates that the injection amount-dependent method is a powerful alternative for rapid analysis of ligand-receptor interactions.

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Design, synthesis, crystal structure, biological evaluation and molecular docking studies of carbazole-arylpiperazine derivatives

Xü

Huang

Shao

et al. 2016

Bioorganic & Medicinal Chemistry

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Subtype-selective α-adrenoceptor (AR) antagonists display optimum therapeutic efficacies for the treatment of benign prostatic hyperplasia (BPH). In this study, we designed and synthesized novel carbazole-arylpiperazines derivatives (1 and 2) on the basis of the proposed pharmacophore model for α-AR antagonists. Structural properties were investigated using single-crystal X-ray diffraction analysis. Comparison of crystal structures with ligand-based pharmacophore models revealed that the two agents may possess antagonistic effects on α subtype. Tissue functional assay in vitro showed that compound 2 exerted strong antagonistic activity on α-AR (pA 7.13) with a poor selectivity for α and α subtypes. Compound 1 exhibited enhanced antagonistic effect on α subtype (pA 7.06) and excellent selectivity for α over α (α/α ratio=79.4). To illustrate the relationship between antagonistic activity and chemical structure, molecular docking studies were performed using the homology models of α receptors. Binding mechanism indicated that small hydrophobic substituents attached to the arylpiperazine moiety were essential for rational design of α-selective antagonists.

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Structural analysis of (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol and binding mechanism with α1A-adrenoceptor: TDDFT calculations, X-ray crystallography and molecular docking

Cited by 4 publications

References 30 publications

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as α 1D -adrenoceptor antagonists

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as α 1D -adrenoceptor antagonists

Rapid analysis of interaction between six drugs and β₂‐adrenergic receptor by injection amount‐dependent method

Design, synthesis, crystal structure, biological evaluation and molecular docking studies of carbazole-arylpiperazine derivatives

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Structural analysis of (S)-1-((1H-benzo[d][1,2,3]triazol-1-yl)oxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol and binding mechanism with α1A-adrenoceptor: TDDFT calculations, X-ray crystallography and molecular docking

Cited by 4 publications

References 30 publications

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as α 1D -adrenoceptor antagonists

Crystal structures, absolute configurations and molecular docking studies of naftopidil enantiomers as α 1D -adrenoceptor antagonists

Rapid analysis of interaction between six drugs and β2‐adrenergic receptor by injection amount‐dependent method

Design, synthesis, crystal structure, biological evaluation and molecular docking studies of carbazole-arylpiperazine derivatives

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Rapid analysis of interaction between six drugs and β₂‐adrenergic receptor by injection amount‐dependent method