Binding mechanism of nine N-phenylpiperazine derivatives and α<sub>1A</sub>-adrenoceptor using site-directed molecular docking and high performance affinity chromatography

Zhao, Xinfeng; Wang, J.; Liu, G. X.; Fan, Tai‐Ping; Zhang, Y. J.; Yu, Jie; Wang, S. X.; Li, Z. J.; Zhang, Y. Y.; Zheng, Xiaohui

doi:10.1039/c5ra10812h

Cited by 6 publications

(3 citation statements)

References 45 publications

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“…Moreover, the possibility of hydrophobic interactions can be operative and decisive also. Quite interestingly, these interactions were in line with the binding mechanism predicted by molecular docking for the interaction of [mCPP] + with serotonin receptor subtypes "5-HT 1A receptor", a major target for research and drug development due to its implication in many physiological processes [41] as well as with the adrenergic receptor; α 1A -adrenoceptor [42]. Furthermore, the piperazine core acts as a hydrogen bonding donating site with crown ether-oxygen atoms through N-H .…”

Section: Membrane Response and Sensitivity Of The Sensorssupporting

confidence: 71%

Potentiometric Signal Transduction for Selective Determination of 1-(3-Chlorophenyl)piperazine “Legal Ecstasy” Through Biomimetic Interaction Mechanism

El-Naby

2019

Chemosensors

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1-(3-chlorophenyl)piperazine (mCPP) is a wide spread new psychoactive substance produces stimulant and hallucinogenic effects similar to those sought from ecstasy. Hence, in the recent years, mCPP has been introduced by the organized crime through the darknet as a part of the illicit ecstasy market with a variable complex profile of pharmacologically active substances that pose problematic risk patterns among people who take these seized products. Accordingly, the design of selective sensors for the determination of mCPP is a very important demand. In this respect, a supramolecular architecture; [Na(15-crown-5)][BPh4] from the assembly of 15-crown-5 and sodium tetraphenylboron has been utilized as an ionophore, for the first time in the selective recognition of mCPP in conjunction with potassium tetrakis(p-chlorophenyl)borate and dioctylphthalate through polymeric membrane ion sensors. The ionophore exhibited a strong binding affinity that resulted in a high sensitivity with a slope closed to the ideal Nernstian value; 58.9 ± 0.43 mV/decade, a larger dynamic range from 10−6 to 10−2 M, a lower limit of detection down to 5.0 × 10−7 M and a fast response time of 5 s. Very important also is it was afforded excellent selectivity towards mCPP over psychoactive substances of major concern, providing a potentially useful system for the determination of mCPP in the illicit market. On comparison with the natural β-cyclodextrin as an ionophore, it exhibited more sensitivity and selectivity estimated to be the superior.

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Section: Membrane Response and Sensitivity Of The Sensorssupporting

confidence: 71%

Potentiometric Signal Transduction for Selective Determination of 1-(3-Chlorophenyl)piperazine “Legal Ecstasy” Through Biomimetic Interaction Mechanism

El-Naby

2019

Chemosensors

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“…4 A and B) both positioned in the hydrophobic pocket involving TM 2, 3, 6 and 7 with the same calculated binding energies (—9.0 kcal/mol). The OH group of ( R )-NAF formed a hydrogen bond (2.6 Å) with Glu190 in the ECL2 region that has been reported to be essential for GPCR activation 23 . The methoxyl at the arylpiperazine moiety formed an H-bond with Thr189 (3.0 Å between the oxygen atom of methoxyl group and the hydroxyl oxygen atom of Thr189).…”

Section: Resultsmentioning

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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“…High-performance affinity chromatography (HPAC) , has been realized as an alternative method for rapid drug–protein interaction analysis with the advantages of good stability and reproducibility, low consumption of protein, and large number of samplings. To pursue the drug–protein interaction, HPAC is commonly performed by frontal analysis − and zonal elution . The two methods are often challenged by the relatively long analysis time and the use of large amounts of drugs as they require saturation of the column by the analytes. , Such issues are partly addressed by nonlinear chromatography, injection amount-dependent assay, and peak profiling approaches. , However, most of the cases have concentrated on the bindings of drugs to serum albumin whereby their feasibility in the other systems remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Affinity Chromatographic Method for Determining Drug–Protein Interaction with Enhanced Speed Than Typical Frontal Analysis

Ou,

Qiao,

et al. 2023

Langmuir

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Revealing drug−protein interaction is highly important to select a drug candidate with improved drug-like properties in the early stages of drug discovery. This highlights the urgent need to develop assays that enable the analysis of drug−protein interaction with high speed. Herein, this purpose was realized by the development of an affinity chromatographic method with a two-fold higher speed than typical assays like frontal analysis and zonal elution. The method involved synthesis of a stationary phase by immobilizing poly(ADPribose) polymerase-1 (PARP 1 ) onto macroporous silica gel through a one-step bioorthogonal reaction, characterization of mutual displacement interaction of two canonical drugs to the immobilized PARP 1 , determination of the interaction between three (iniparib, rucaparib, and olaparib) drugs and the protein, and validation of these parameters by typical frontal analysis. The numbers of binding sites on the column were (2.85 ± 0.05) × 10 −7 , (1.89 ± 0.71) × 10 −6 , and (1.49 ± 0.06) × 10 −7 M for iniparib, rucaparib, and olaparib, respectively. On these sites, the association constants of the three drugs to the protein were (9.85 ± 0.56) × 10 4 , (2.85 ± 0.34) × 10 4 , and (1.07 ± 0.35) × 10 5 M −1 . The determined parameters presented a good agreement with the calculation by typical frontal analyses, which indicated that the current continuous competitive frontal analysis method was reliable for determining drug−protein interaction. Application of the methods was achieved by screening tubeimosides I and II as the bioactive compounds against breast cancer in Bolbostemma paniculatum. Their mechanism may be the interference of DNA repair via down-regulating PARP 1 and meiotic recombination 11 expressions, thus leading to oncogene mutations and death of cancer cells. The method was high speed since it allowed simultaneous determination of binding parameters between two drugs and a protein with a smaller number of experiments to be performed. Such a feature made the method an attractive alternative for high-speed analysis of drug−protein interaction or the other bindings in a binary system.

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Binding mechanism of nine N-phenylpiperazine derivatives and α_1A-adrenoceptor using site-directed molecular docking and high performance affinity chromatography

Abstract: Investigating the binding mechanism of α1A-adrenoceptor and its specific ligands by affinity chromatography.

Cited by 6 publications

References 45 publications

Potentiometric Signal Transduction for Selective Determination of 1-(3-Chlorophenyl)piperazine “Legal Ecstasy” Through Biomimetic Interaction Mechanism

Potentiometric Signal Transduction for Selective Determination of 1-(3-Chlorophenyl)piperazine “Legal Ecstasy” Through Biomimetic Interaction Mechanism

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

Affinity Chromatographic Method for Determining Drug–Protein Interaction with Enhanced Speed Than Typical Frontal Analysis

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Binding mechanism of nine N-phenylpiperazine derivatives and α1A-adrenoceptor using site-directed molecular docking and high performance affinity chromatography

Abstract: Investigating the binding mechanism of α1A-adrenoceptor and its specific ligands by affinity chromatography.

Cited by 6 publications

References 45 publications

Potentiometric Signal Transduction for Selective Determination of 1-(3-Chlorophenyl)piperazine “Legal Ecstasy” Through Biomimetic Interaction Mechanism

Potentiometric Signal Transduction for Selective Determination of 1-(3-Chlorophenyl)piperazine “Legal Ecstasy” Through Biomimetic Interaction Mechanism

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

Affinity Chromatographic Method for Determining Drug–Protein Interaction with Enhanced Speed Than Typical Frontal Analysis

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Binding mechanism of nine N-phenylpiperazine derivatives and α_1A-adrenoceptor using site-directed molecular docking and high performance affinity chromatography