Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1)
Voolstra, Christian R.
KAUST DepartmentRed Sea Research Center (RSRC)
Biological and Environmental Sciences and Engineering (BESE) Division
Permanent link to this recordhttp://hdl.handle.net/10754/602279
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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.
CitationAlkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1) 2016, 14 (2):28 Marine Drugs
SponsorsResearch 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.
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