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

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

1
School of Pharmacy, Nanjing Medical University, Nanjing 210029, China
2
Department of Internal Neurology, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing 210008, China
3
School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
*
Authors to whom correspondence should be addressed.
Received: 16 March 2014 / Revised: 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. View Full-Text
Keywords: neuronal nitric oxide synthase; inhibitors; pharmacophore; virtual screening; docking neuronal nitric oxide synthase; inhibitors; pharmacophore; virtual screening; docking
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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