QSAR studies of aminopeptidase N/CD13 (APN) inhibitors with the scaffold 3-phenylpropane-1,2-diamine and molecular docking

Xu, Yingying; Zhang, Lei; Li, Minyong; Xu, Wenfang; Fang, Hao; Shang, Luqing

doi:10.1007/s00044-011-9597-1

Cited by 4 publications

(2 citation statements)

References 36 publications

(22 reference statements)

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“…While overviewing the previously performed QSAR studies [60][61][62][63][64][65][66][67][68][69], it is observed that there are a few common features present namely electronegative and electropositive substitutions, hydrophobicity, steric properties, molecular symmetry, atomic masses and hydrogen bond donor-acceptor features which are responsible for the fluctuation in the potency of the APN inhibitors. Our previous study on 175 diverse set of APN inhibitors [63] disclosed that a few molecular features of the APN inhibitors namely the positive ionizable, hydrogen bond donor-acceptor and ring aromatic features of molecules are some of the important molecular features have important roles in determining the APN inhibitory activity of these molecules [63].…”

Section: Comparison Of the Previously Performed Qsar Studies With Thementioning

confidence: 99%

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Banerjee

Amin

Baidya

et al. 2020

SAR and QSAR in Environmental Research

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The zinc-dependent enzyme aminopeptidase N (APN) is a member of the M1 metalloenzyme family. The multi-functionality of APN as a peptidase, a receptor and a signalling molecule has provided it the access to influence a number of disease conditions namely viral diseases, angiogenesis, cellular metastasis and invasion including different cancer conditions. Hence, the development of potent APN inhibitors is a possible route for the treatment of diseases related to the activity of APN. In this study, different QSAR approaches have been adopted to identify the structural features of a group of hydroxamate-based ureido-amino acid derivative APN inhibitors. This study was able to identify different constitutional aspects of these APN inhibitors which are important for their inhibitory potency. Additionally, some of these observations were also aligned with the observations of previously performed QSAR studies conducted on different APN inhibitors. Therefore, the results of this study may help to design potent and effective APN inhibitors in the future. ARTICLE HISTORY

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Section: Comparison Of the Previously Performed Qsar Studies With Thementioning

confidence: 99%

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Banerjee

Amin

Baidya

et al. 2020

SAR and QSAR in Environmental Research

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“…Therefore, model 1 was selected as the best MIFs model. Compared with the QSAR results of literature, our 3D-QSAR modeling have good predictive ability (Zhu et al, 2008;Xu et al, 2012).…”

Section: Molecular Docking and MD Simulationsmentioning

confidence: 65%

3D-QSAR Studies, Molecular Dynamics Simulation and Free Energy Calculation of APN Inhibitors

Qu¹,

Tang²,

Kuang³

et al. 2015

International J. of Pharmacology

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The MIFs was applied to a data set of 40 N-phenylhomophthalimide derivatives of APN inhibitors to generate the 3D-QSAR model at various 3D grid spacing. The cross-validated correlation coefficient q 2 LMO (0.6204) and r 2 pred (0.9810) were obtained at a 1.0 Å 3D grid spacing, indicating the statistical significance of this class of compounds. The calculated inhibitive activities showed a high degree of agreement with experimented values. Then, the 6 nsec MD simulation of proteinligand complex and binding free energy analysis were carried out. The stable binding mode of the most active compound 21 was determined.

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Rapid screening of aminopeptidase N inhibitors by capillary electrophoresis with electrophoretically mediated microanalysis

Wang

Cao

et al. 2014

Electrophoresis

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In this work, an electrophoretically mediated microanalysis (EMMA) method with a partial-filling technique was setup to evaluate the inhibitory potency of novel compounds toward aminopeptidase N (APN). It was necessary to optimize the electrophoretic conditions with respect to the kinetic constraints and for attaining high sensitivity. In our setup, a part of the capillary was filled with the incubation buffer for the enzyme reaction, whereas the rest was filled with a suitable BGE for the separation of substrates and products. To monitor the performance of the newly developed method, the kinetic constants (Km and Vmax) for the catalyzed dissociation of L-Leucine-p-nitroanilide in the presence of APN as well as the inhibition constant (IC50 ) of a known competitive inhibitor, that is bestatin, were determined and these results were compared with those obtained by a classical spectrophotometric assay. The developed EMMA method was subsequently applied to the screening of 30 APN inhibitors. Whereas the inhibition potency of these inhibitors (expressed in IC50 values) were significantly underestimated by the EMMA method, the order of the inhibitory potential of these various compounds was found in agreement with the literature.

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QSAR studies of aminopeptidase N/CD13 (APN) inhibitors with the scaffold 3-phenylpropane-1,2-diamine and molecular docking

Cited by 4 publications

References 36 publications

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

3D-QSAR Studies, Molecular Dynamics Simulation and Free Energy Calculation of APN Inhibitors

Rapid screening of aminopeptidase N inhibitors by capillary electrophoresis with electrophoretically mediated microanalysis

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