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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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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. |
format | Online Article Text |
id | pubmed-4771981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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