Denzil R. Beukes

Antiplasmodial halogenated monoterpenes from the marine red alga Plocamium cornutum.

In our continuing search for antimalarial leads from South African marine organisms we have examined the antiplasmodial organic extracts of the endemic marine red alga Plocamium cornutum (Turner) Harvey. Two new and three known halogenated monoterpenes were isolated and their structures determined by standard spectroscopic techniques. The 3,7-dimethyl-3,4-dichloro-octa-1,5,7-triene skeleton is common to all five compounds. Interestingly, compounds bearing the 7-dichloromethyl substituent showed significantly higher antiplasmodial activity toward a chloroquine sensitive strain of Plasmodium falciparum.

Fucoxanthin, Tetraprenylated Toluquinone and Toluhydroquinone Metabolites from Sargassum heterophyllum Inhibit the in vitro Growth of the Malaria Parasite Plasmodium falciparum

Abstract In the course of our search for antimalarial leads from marine algae, four metabolites, sargaquinoic acid, sargahydroquinoic acid, sargaquinal and fucoxanthin, were isolated from the South African alga Sargassum heterophyllum. Fucoxanthin and sargaquinal showed good antiplasmodial activity toward a chloroquine-sensitive strain (D10) of Plasmodium falciparum (IC50 1.5 and 2.0 μm, respectively), while sargaquinoic acid and sargahydroquinoic acid were only moderately active (IC50 12.0 and 15.2 μm, respectively).

Quinones and halogenated monoterpenes of algal origin show anti-proliferative effects against breast cancer cells in vitro

SummaryRed and brown algae have been shown to produce a variety of compounds with chemotherapeutic potential. A recent report described the isolation of a range of novel polyhalogenated monoterpene compounds from the red algae Plocamium corallorhiza and Plocamium cornutum collected off the coast of South Africa, together with the previously described tetraprenylquinone, sargaquinoic acid (SQA), from the brown algae Sargassum heterophyllum. In our study, the algal compounds were screened for anti-proliferative activity against metastatic MDA-MB-231 breast cancer cells revealing that a number of compounds displayed anti-cancer activity with IC50 values in the micromolar range. A subset of the compounds was tested for differential toxicity in the MCF-7/MCF12A system and five of these, including sargaquinoic acid, were found to be at least three times more toxic to the breast cancer than the non-malignant cell line. SQA was further analysed in terms of its mechanism of cytotoxicity in MDA-MB-231 cells. The ability to initiate apoptosis was distinguished from the induction of an inflammatory necrotic response via flow cytometry with propidium iodide and Hoescht staining, confocal microscopy with Annexin V and propidium iodide staining as well as the PARP cleavage assay. We report that SQA induced apoptosis while a polyhalogenated monoterpene RU015 induced necrosis in metastatic breast cancer cells in vitro. Furthermore, we demonstrated that apoptosis induction by SQA occurs via caspase-3, -6, -8, -9 and -13 and was associated with down-regulation of Bcl-2. In addition, cell cycle analyses revealed that the compound causes G1 arrest in MDA-MB-231 cells.

Identification and in vitro anti-esophageal cancer activity of a series of halogenated monoterpenes isolated from the South African seaweeds Plocamium suhrii and Plocamium cornutum

Five known (1, 2, 4, 6 and 7) halogenated monoterpenes together with 1Z,3R∗,4S∗,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene (3) and (3R∗,4S∗)-3,4,6,7-tetrachloro-3,7-dimethyl-octen-1-ene (5) were isolated from the red macroalga Plocamium suhrii and their structures deduced from their spectroscopic data. The seven compounds from P. suhrii together with five related compounds from Plocamium cornutum have been evaluated for their cytotoxic effects on an esophageal cancer cell line (WHCO1). Compounds 1-6 showed greater cytotoxicity in this assay as compared to the known anticancer drug cisplatin.

Assessment of potential anti-cancer stem cell activity of marine algal compounds using an in vitro mammosphere assay

BackgroundThe cancer stem cell (CSC) theory proposes that tumours arise from and are sustained by a subpopulation of cells with both cancer and stem cell properties. One of the key hallmarks of CSCs is the ability to grow anchorage-independently under serum-free culture conditions resulting in the formation of tumourspheres. It has further been reported that these cells are resistant to traditional chemotherapeutic agents.MethodsIn this study, the tumoursphere assay was validated in MCF-7 cells and used to screen novel marine algal compounds for potential anti-cancer stem cell (CSC) activity in vitro.ResultsMCF-7 breast cancer cells were observed to generate tumourspheres or mammospheres after 3-5 days growth in anchorage-independent conditions and an apparent enrichment in potential CSCs was observed by an increase in the proportion of CD44high/CD24low marker-bearing cells and Oct4 expression compared to those in the bulk population grown in regular adherent conditions. Using this assay, a set of algal metabolites was screened for the ability to inhibit mammosphere development as a measure of potential anti-CSC activity. We report that the polyhalogenated monoterpene stereoisomers RU017 and RU018 isolated from the red alga Plocamium cornutum, both of which displayed no cytotoxicity against either adherent MCF-7 breast cancer or MCF-12A non-transformed breast epithelial cells, were able to prevent MCF-7 mammosphere formation in vitro. On the other hand, neither the brown algal carotenoid fucoxanthin nor the chemotherapeutic paclitaxel, both of which were toxic to adherent MCF-7 and MCF-12A cells, were able to inhibit mammosphere formation. In fact, pre-treatment with paclitaxel appeared to enhance mammosphere formation and development, a finding which is consistent with the reported resistance of CSCs to traditional chemotherapeutic agents.ConclusionDue to the proposed clinical significance of CSC in terms of tumour initiation and metastasis, the identification of agents able to inhibit this subpopulation has clinical significance.

Novel polypropionates from the South African marine mollusc Siphonaria capensis

Abstract The endemic South African pulmonate mollusc Siphonaria capensis yielded C-2 epimeric mixtures of the known polypropionate metabolites siphonarienfuranone ( 1 ) and its Z-isomer ( 2 ), and three new polypropionates, capensinone ( 3 ), capensifuranone ( 4 ) and (2E, 4S, 6S, 8S)-2,4,6,8-tetramethyl-2-undecenoic acid ( 5 ).

Antiplasmodial and antimicrobial activities of South African marine algal extracts.

Seventy-eight crude organic fractions from nineteen species of marine algae collected from the coast of South Africa were screened for activity against a chloroquine sensitive strain of Plasmodium falciparum (D10), Staphylococcus aureus, Klebsiella pneumoniae, Mycobacterium aurum and Candida albicans. Fifteen crude fractions showed good antiplasmodical activity (IC50 <10 μg/mL). The dichloromethane fraction from Sargassum heterophyllum (Turner) C. Agardh (Sargassaceae) was the most active with an IC50 value of 2.8 μg/mL. Eleven extracts showed MIC values ≤ 1 mg/mL against at least one of S. aureus, K. pneumoniae, M. aurum and C. albicans. The broadest spectrum of antimicrobial activity was exhibited by the aqueous-HP20 fraction of Polysiphonia incompta Harvey (Rhodomelaceae). This study shows that marine algae not only produce antimicrobial compounds but also may be a source of antimalarial lead compounds.

Enhanced Antimicrobial and Anticancer Activity of Silver and Gold Nanoparticles Synthesised Using Sargassum incisifolium Aqueous Extracts

A detailed, methodical approach was used to synthesise silver and gold nanoparticles using two differently prepared aqueous extracts of the brown algae Sargassum incisifolium. The efficiency of the extracts in producing nanoparticles were compared to commercially available brown algal fucoidans, a major constituent of brown algal aqueous extracts. The nanoparticles were characterised using TEM, XRD and UV/Vis spectroscopy and zeta potential measurements. The rate of nanoparticle formation was assessed using UV/Vis spectroscopy and related to the size, shape and morphology of the nanoparticles as revealed by TEM. The antioxidant, reducing power and total polyphenolic contents of the aqueous extracts and fucoidans were determined, revealing that the aqueous extracts with the highest contents produced smaller, spherical, more monodisperse nanoparticles at a faster rate. The nanoparticles were assessed against two gram-negative bacteria, two gram-positive bacteria and one yeast strain. In contrast to the literature, the silver nanoparticles produced using the aqueous extracts were particularly toxic to Gram-negative bacteria, while the gold nanoparticles lacked activity. The cytotoxic activity of the nanoparticles was also evaluated against cancerous (HT-29, MCF-7) and non-cancerous (MCF-12a) cell lines. The silver nanoparticles displayed selectivity, since the MCF-12a cell line was found to be resistant to the nanoparticles, while the cancerous HT-29 cell line was found to be sensitive (10% viability). The gold nanoparticles displayed negligible toxicity.

Isolation, Characterization and Antiproliferative Activity of New Metabolites from the South African Endemic Red Algal Species Laurencia alfredensis

The marine red algae of the genus Laurencia have been widely studied for their structurally diverse and biologically active secondary metabolites. We report here the natural product investigation of the organic extract of a newly identified South African endemic species, Laurencia alfredensis. A sequence of column chromatography, preparative TLC and normal phase HPLC resulted in the isolation of eleven compounds comprising three labdane-type diterpenes (1–3), four polyether triterpenes (4–7), three cholestane-type ecdysteroids (8–10) and a glycolipid (11). Compounds 1–3, 5–8 and 10 have not previously been reported, while compound 9 is reported here for the first time from a natural source and the known compound 11 isolated for the first time from the genus Laurencia. The structural elucidation and the relative configuration assignments of the compounds were accomplished by extensive use of 1D- and 2D-NMR, HR-ESI-MS, UV and IR spectroscopic techniques, while the absolute configuration of compound 1 was determined by single-crystal X-ray diffraction analysis. All compounds were evaluated against the MDA-MB-231 breast and HeLa cervical cancer cell lines. Compound 2 exhibited low micromolar antiproliferative activity (IC50 = 9.3 µM) against the triple negative breast carcinoma and compound 7 was similarly active (IC50 = 8.8 µM) against the cervical cancer cell line.

Very Green Photosynthesis of Gold Nanoparticles by a Living Aquatic Plant: Photoreduction of AuIII by the Seaweed Ulva armoricana

Light-assisted in vivo synthesis of gold nanoparticles (NPs) from aqueous solutions of dilute AuIII salts by a living green marine seaweed (Ulva armoricana) is reported for the first time. NPs synthesised using typical procedures have many associated environmental hazards. The reported methods involve green, nontoxic, eco-friendly synthetic procedures. The formation of AuNPs was extremely rapid (≈15 min) following illumination of the living U. armoricana, while the rate of NP formation in the dark was very slow (over 2 weeks). The properties of the AuNPs formed were confirmed using a battery of spectroscopic techniques. U. armoricana were found to be very efficient in Au0 uptake, and this, together with the rapid formation of AuNPs under illumination, indicated that the seaweed remained living during NP formation. The TEM images supported this, revealing that the thylakoid membranes and cell structure remained intact. The AuNPs formed on the surface of U. armoricana thallus, along the cell walls and in the chloroplasts. Without further workup, the dried, U. armoricana-supported AuNPs were efficient in the catalytic reduction of 4-nitrophenol, demonstrating the completely green cycle of AuNP formation and catalytic activity. The results mean that an aquatic plant growing in water rich in gold salts could bio-accumulate AuNPs from its aquatic environment, simply with the activation of sunlight.