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Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)

The sponge Stylissa carteri is known to produce a number of secondary metabolites displaying anti-fouling, anti-inflammatory, and anti-cancer activity. However, the anti-viral potential of metabolites produced by S. carteri has not been extensively explored. In this study, an S. carteri extract was...

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Autores principales: O’Rourke, Aubrie, Kremb, Stephan, Bader, Theresa Maria, Helfer, Markus, Schmitt-Kopplin, Philippe, Gerwick, William H., Brack-Werner, Ruth, Voolstra, Christian R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771981/
https://www.ncbi.nlm.nih.gov/pubmed/26861355
http://dx.doi.org/10.3390/md14020028
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author O’Rourke, Aubrie
Kremb, Stephan
Bader, Theresa Maria
Helfer, Markus
Schmitt-Kopplin, Philippe
Gerwick, William H.
Brack-Werner, Ruth
Voolstra, Christian R.
author_facet O’Rourke, Aubrie
Kremb, Stephan
Bader, Theresa Maria
Helfer, Markus
Schmitt-Kopplin, Philippe
Gerwick, William H.
Brack-Werner, Ruth
Voolstra, Christian R.
author_sort O’Rourke, Aubrie
collection PubMed
description The sponge Stylissa carteri is known to produce a number of secondary metabolites displaying anti-fouling, anti-inflammatory, and anti-cancer activity. However, the anti-viral potential of metabolites produced by S. carteri has not been extensively explored. In this study, an S. carteri extract was HPLC fractionated and a cell based assay was used to evaluate the effects of HPLC fractions on parameters of Human Immunodeficiency Virus (HIV-1) infection and cell viability. Candidate HIV-1 inhibitory fractions were then analyzed for the presence of potential HIV-1 inhibitory compounds by mass spectrometry, leading to the identification of three previously characterized compounds, i.e., debromohymenialdisine (DBH), hymenialdisine (HD), and oroidin. Commercially available purified versions of these molecules were re-tested to assess their antiviral potential in greater detail. Specifically, DBH and HD exhibit a 30%–40% inhibition of HIV-1 at 3.1 μM and 13 μM, respectively; however, both exhibited cytotoxicity. Conversely, oroidin displayed a 50% inhibition of viral replication at 50 μM with no associated toxicity. Additional experimentation using a biochemical assay revealed that oroidin inhibited the activity of the HIV-1 Reverse Transcriptase up to 90% at 25 μM. Taken together, the chemical search space was narrowed and previously isolated compounds with an unexplored anti-viral potential were found. Our results support exploration of marine natural products for anti-viral drug discovery.
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spelling pubmed-47719812016-03-08 Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1) O’Rourke, Aubrie Kremb, Stephan Bader, Theresa Maria Helfer, Markus Schmitt-Kopplin, Philippe Gerwick, William H. Brack-Werner, Ruth Voolstra, Christian R. Mar Drugs Article The sponge Stylissa carteri is known to produce a number of secondary metabolites displaying anti-fouling, anti-inflammatory, and anti-cancer activity. However, the anti-viral potential of metabolites produced by S. carteri has not been extensively explored. In this study, an S. carteri extract was HPLC fractionated and a cell based assay was used to evaluate the effects of HPLC fractions on parameters of Human Immunodeficiency Virus (HIV-1) infection and cell viability. Candidate HIV-1 inhibitory fractions were then analyzed for the presence of potential HIV-1 inhibitory compounds by mass spectrometry, leading to the identification of three previously characterized compounds, i.e., debromohymenialdisine (DBH), hymenialdisine (HD), and oroidin. Commercially available purified versions of these molecules were re-tested to assess their antiviral potential in greater detail. Specifically, DBH and HD exhibit a 30%–40% inhibition of HIV-1 at 3.1 μM and 13 μM, respectively; however, both exhibited cytotoxicity. Conversely, oroidin displayed a 50% inhibition of viral replication at 50 μM with no associated toxicity. Additional experimentation using a biochemical assay revealed that oroidin inhibited the activity of the HIV-1 Reverse Transcriptase up to 90% at 25 μM. Taken together, the chemical search space was narrowed and previously isolated compounds with an unexplored anti-viral potential were found. Our results support exploration of marine natural products for anti-viral drug discovery. MDPI 2016-02-04 /pmc/articles/PMC4771981/ /pubmed/26861355 http://dx.doi.org/10.3390/md14020028 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
O’Rourke, Aubrie
Kremb, Stephan
Bader, Theresa Maria
Helfer, Markus
Schmitt-Kopplin, Philippe
Gerwick, William H.
Brack-Werner, Ruth
Voolstra, Christian R.
Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)
title Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)
title_full Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)
title_fullStr Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)
title_full_unstemmed Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)
title_short Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)
title_sort alkaloids from the sponge stylissa carteri present prospective scaffolds for the inhibition of human immunodeficiency virus 1 (hiv-1)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4771981/
https://www.ncbi.nlm.nih.gov/pubmed/26861355
http://dx.doi.org/10.3390/md14020028
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