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

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.

Ethanol Extract of Stylissa carteri Induces Cell Death in Parental and Paclitaxel-Resistant Cervical Cancer Cells

“…12 In addition, alkaloid contained in sponge extract has significant role as the inhibitor of ubiquitin enzyme complex formation with proteasome that will p53 activity to lower the excessive cell proliferation activity in cancer cells and also cause apoptosis induction for proliferated cells. 6,12 An evaluation of Stylissa carteri extract as their potential as anticancer agent has been conducted. Stylissa carteri ethanol extracts were treated toward parental HeLa cells and also paclitaxel-resistant HeLa cells.…”

“…Stylissa carteri, a marine sponge which is widely distributed in the Indonesian Exclusive Economic Zone (EEZ), has been recognized for its therapeutic potentials, especially for its anticancer properties. 6 Based on our previous studies, ethanol extract of Stylissa carteri has been proven to induce cell death and to inhibit the cell proliferation of colon cancer cell lines as well as breast cancer cell lines (unpublished data). Hence, Stylissa carteri is thought to have a potential to target cervical cancer cells.…”

Science, Diplomacy, and the Red Sea’s Unique Coral Reef: It’s Time for Action

“…Its unique reefs are also a rich potential source of natural products and medicines (Shaala et al, 2015;Ibrahim et al, 2017). The high degree of endemism and adaptation to high salinity and high temperature could potentially have led to the appearance of unique molecules and metabolites not to be found in other reef systems of the world (O'Rourke et al, 2016(O'Rourke et al, , 2018Kremb et al, 2017). The biodiversity that is found only on healthy reefs is considered by scientists to be key to finding new medicines for the 21st century.…”

Advanced identification of global bioactivity hotspots via screening of the metabolic fingerprint of entire ecosystems

“…Another strategy for the identification of NP candidates with promise is the screening for antiviral activities, such as inhibition of the human immunodeficiency virus type-1 (HIV-1). This has been successfully demonstrated for a broad variety of complex mixtures of natural products, using a robust phenotypic screening assay encompassing the entire HIV replication cycle (EASY-HIT) [22][23][24][25][26] .…”