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Int. J. Mol. Sci. 2014, 15(5), 8553-8569; doi:10.3390/ijms15058553
Article

The Discovery of Potentially Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: A Combination of Pharmacophore Modelling, CoMFA, Virtual Screening and Molecular Docking Studies

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Received: 16 March 2014; in revised form: 30 April 2014 / Accepted: 6 May 2014 / Published: 14 May 2014
(This article belongs to the Special Issue Molecular Science for Drug Development and Biomedicine)
Abstract: Neuronal nitric oxide synthase (nNOS) plays an important role in neurotransmission and smooth muscle relaxation. Selective inhibition of nNOS over its other isozymes is highly desirable for the treatment of neurodegenerative diseases to avoid undesirable effects. In this study, we present a workflow for the identification and prioritization of compounds as potentially selective human nNOS inhibitors. Three-dimensional pharmacophore models were constructed based on a set of known nNOS inhibitors. The pharmacophore models were evaluated by Pareto surface and CoMFA (Comparative Molecular Field Analysis) analyses. The best pharmacophore model, which included 7 pharmacophore features, was used as a search query in the SPECS database (SPECS®, Delft, The Netherlands). The hit compounds were further filtered by scoring and docking. Ten hits were identified as potential selective nNOS inhibitors.
Keywords: neuronal nitric oxide synthase; inhibitors; pharmacophore; virtual screening; docking neuronal nitric oxide synthase; inhibitors; pharmacophore; virtual screening; docking
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Xu, G.; Chen, Y.; Shen, K.; Wang, X.; Li, F.; He, Y. The Discovery of Potentially Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: A Combination of Pharmacophore Modelling, CoMFA, Virtual Screening and Molecular Docking Studies. Int. J. Mol. Sci. 2014, 15, 8553-8569.

AMA Style

Xu G, Chen Y, Shen K, Wang X, Li F, He Y. The Discovery of Potentially Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: A Combination of Pharmacophore Modelling, CoMFA, Virtual Screening and Molecular Docking Studies. International Journal of Molecular Sciences. 2014; 15(5):8553-8569.

Chicago/Turabian Style

Xu, Guanhong; Chen, Yue; Shen, Kun; Wang, Xiuzhen; Li, Fei; He, Yan. 2014. "The Discovery of Potentially Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: A Combination of Pharmacophore Modelling, CoMFA, Virtual Screening and Molecular Docking Studies." Int. J. Mol. Sci. 15, no. 5: 8553-8569.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert