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

Marine Drugs

卷:14

Ruth Brack-Werner¹  Markus Helfer¹  Aubrie O’Rourke²  Stephan Kremb²  Christian R. Voolstra²  Theresa Maria Bader³  Philippe Schmitt-Kopplin³  William H. Gerwick⁴ 

[1] Institute of Virology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany;

[2] Red Sea Research Center, Division of Biological and Environmental Science and Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia;

[3] Research Unit Analytical BioGeoChemistry, Helmholtz Zentrum Muenchen, 85764 Neuherberg, Germany;

[4] Scripps Institution of Oceanography and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA;

关键词: Stylissa carteri;    marine bioprospecting;    HIV-1;    reverse transcriptase;    Red Sea;   

DOI  :  10.3390/md14020028

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown