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

Handle URI:
http://hdl.handle.net/10754/602279
Title:
Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)
Authors:
O’Rourke, Aubrie; Kremb, Stephan; Bader, Theresa; Helfer, Markus; Schmitt-Kopplin, Philippe; Gerwick, William; Brack-Werner, Ruth; Voolstra, Christian R. ( 0000-0003-4555-3795 )
Abstract:
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.
KAUST Department:
Red Sea Research Center (RSRC); Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1) 2016, 14 (2):28 Marine Drugs
Publisher:
MDPI AG
Journal:
Marine Drugs
Issue Date:
4-Feb-2016
DOI:
10.3390/md14020028
Type:
Article
ISSN:
1660-3397
Sponsors:
Research reported in this publication was supported by baseline research funds to Christian R. Voolstra and an AEA3 award by the King Abdullah University of Science and Technology (KAUST). Thank you to Najeh Kharbatia and Salim Sioud, technical staff at the Analytical Core Lab at KAUST, and thank you to the staff of the Coastal and Marine Resources Core Lab (CMOR) for providing boat access. Thank you to Nicole de Voogd for assisting with sponge specimen taxonomic identification. Thank you to Martha Schneider for providing selection and experimental data on the effects of two reference cytotoxic compounds, Doxorubicin and Staurosporine, on the HIV infection signal and the metabolic activity in LC5-RIC cells.
Additional Links:
http://www.mdpi.com/1660-3397/14/2/28
Appears in Collections:
Articles; Red Sea Research Center (RSRC); Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorO’Rourke, Aubrieen
dc.contributor.authorKremb, Stephanen
dc.contributor.authorBader, Theresaen
dc.contributor.authorHelfer, Markusen
dc.contributor.authorSchmitt-Kopplin, Philippeen
dc.contributor.authorGerwick, Williamen
dc.contributor.authorBrack-Werner, Ruthen
dc.contributor.authorVoolstra, Christian R.en
dc.date.accessioned2016-03-20T14:01:07Zen
dc.date.available2016-03-20T14:01:07Zen
dc.date.issued2016-02-04en
dc.identifier.citationAlkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1) 2016, 14 (2):28 Marine Drugsen
dc.identifier.issn1660-3397en
dc.identifier.doi10.3390/md14020028en
dc.identifier.urihttp://hdl.handle.net/10754/602279en
dc.description.abstractThe 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.en
dc.description.sponsorshipResearch reported in this publication was supported by baseline research funds to Christian R. Voolstra and an AEA3 award by the King Abdullah University of Science and Technology (KAUST). Thank you to Najeh Kharbatia and Salim Sioud, technical staff at the Analytical Core Lab at KAUST, and thank you to the staff of the Coastal and Marine Resources Core Lab (CMOR) for providing boat access. Thank you to Nicole de Voogd for assisting with sponge specimen taxonomic identification. Thank you to Martha Schneider for providing selection and experimental data on the effects of two reference cytotoxic compounds, Doxorubicin and Staurosporine, on the HIV infection signal and the metabolic activity in LC5-RIC cells.en
dc.language.isoenen
dc.publisherMDPI AGen
dc.relation.urlhttp://www.mdpi.com/1660-3397/14/2/28en
dc.rightsThis is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectStylissa carterien
dc.subjectmarine bioprospectingen
dc.subjectHIV-1en
dc.subjectreverse transcriptaseen
dc.subjectRed Seaen
dc.titleAlkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)en
dc.typeArticleen
dc.contributor.departmentRed Sea Research Center (RSRC)en
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalMarine Drugsen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionResearch Unit Analytical BioGeoChemistry, Helmholtz Zentrum Muenchen, 85764 Neuherberg, Germanyen
dc.contributor.institutionInstitute of Virology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germanyen
dc.contributor.institutionAnalytical Food Chemistry, Technical University of Munich, 85354 Freising Weihenstephan, Germanyen
dc.contributor.institutionScripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USAen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
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