Green Synthesized sAuNPs as a Potential Delivery Platform for Cytotoxic Alkaloids.

The use of natural products as chemotherapeutic agents is well established. However, many are associated with undesirable side effects, including high toxicity and instability. Previous reports on the cytotoxic activity of pyrroloiminoquinones isolated from Latrunculid sponges against cancer cell lines revealed extraordinary activity at IC50 of 77nM for discorhabdins. Their general lack of selectivity against the cancer and normal cell lines, however, precludes further development. In this study, extraction of a South African Latrunculid sponge produced three known pyrroloiminoquinone metabolites (14-bromodiscorhabdin C (5), Tsitsikammamine A (6) and B (7)). The assignment of the structures was established using standard 1D and 2D NMR experiments. To mitigate the lack of selectivity, the compounds were loaded onto gold nanoparticles synthesized using the aqueous extract of a brown seaweed, Sargassum incisifolium (sAuNPs). The cytotoxicity of the metabolites alone, and their sAuNP conjugates, were evaluated together with the known anticancer agent doxorubicin and its AuNP conjugate. The compound-AuNP conjugates retained their strong cytotoxic activity against the MCF-7 cell line, with >90% of the pyrroloiminoquinone-loaded AuNPs penetrating the cell membrane. Loading cytotoxic natural products onto AuNPs provides an avenue in overcoming some issues hampering the development of new anticancer drugs.

ROV assessment of mesophotic fish and associated habitats across the continental shelf of the Amathole region.

Understanding how fish associate with habitats across marine landscapes is crucial to developing effective marine spatial planning (MSP) in an expanding and diversifying ocean economy. Globally, anthropogenic pressures impact the barely understood temperate mesophotic ecosystems and South Africa's remote Amathole shelf is no exception. The Kei and East London region encompass three coastal marine protected areas (MPAs), two of which were recently extended to the shelf-edge. The strong Agulhas current (exceeding 3 m/s), which runs along the narrow shelf exacerbates sampling challenges. For the first time, a remotely operated vehicle (ROV) surveyed fish and their associated habitats across the shelf. Results indicated fish assemblages differed between the two principle sampling areas, and across the shelf. The number of distinct fish assemblages was higher inshore and on the shelf-edge, relative to the mid-shelf. However, the mid-shelf had the highest species richness. Unique visuals of rare Rhinobatos ocellatus (Speckled guitarfish) and shoaling Polyprion americanus (wreckfish) were collected. Visual evidence of rhodolith beds, deep-water lace corals and critically endangered endemic seabreams were ecologically important observations. The ROV enabled in situ sampling without damaging sensitive habitats or extracting fish. This study provided information that supported the Amathole MPA expansions, which extended protection from the coast to beyond the shelf-edge and will guide their management. The data gathered provides baseline information for future benthopelagic fish and habitat monitoring in these new MPAs.

Encapsulation of Variabilin in Stearic Acid Solid Lipid Nanoparticles Enhances Its Anticancer Activity in Vitro.

The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 µM vs. 8.94 µM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 µM for variabilin, Var-SLN and Ceramide, respectively. These samples revealed no activity (>100 µM for all) against HT-29 (colon) cell lines and MCF-12 (normal breast) cell lines. Var-SLNs induced 47, 48 and 59% of apoptosis in HT-29, MCF-7 and PC-3 cells, respectively, while variabilin alone revealed 38, 29 and 29% apoptotic cells for HT-29, MCF-7 and PC-3 cell lines, respectively. The encapsulation of natural products into SLNs may provide a promising approach to overcome some of the issues hindering the development of new anticancer drugs from natural products.

Makaluvic acids from the South African latrunculid sponge Strongylodesma aliwaliensis.

Two new metabolites, makaluvic acid C (1) and N-1-beta-d-ribofuranosylmakaluvic acid C (2), were isolated from the recently described sponge Strongylodesma aliwaliensis collected off the east coast of South Africa. Standard spectroscopic techniques provided the structures of both compounds. Chiral GC analysis of the peracetylated aldononitrile derivative of the acid hydrolysate of 2 confirmed the d-configuration of the ribose moiety in this compound. Compound 2 and four related pyrroloquinoline metabolites, isolated previously from S. aliwaliensis, exhibited in vitro cytotoxicity against esophageal cancer cells.

Antiesophageal cancer activity from Southern African marine organisms.

Squamous cell esophageal cancer presents a significant health burden in many developing countries around the world. In South Africa, this disease is one of the most common causes of cancer-related deaths in black males. Because this cancer is only modestly responsive to available chemotherapeutic agents, there is a need to develop more effective therapeutic agents for this cancer. Marine organisms are currently regarded as a promising source of unique bioactive molecules because they display a rich diversity of secondary metabolites. Some of these compounds have significant anticancer activity, with a few of these currently in phase I and II clinical trials. We report here an ongoing program to screen marine organisms collected from subtidal benthic communities off the coast of southern Africa for activity against cultured esophageal cancer cells. Of the 137 extracts tested, 2.2% displayed high activity (score = 3) and 11.7% displayed moderate activity (score = 2) against cultured esophageal cancer cells. Our results suggest that sponges had a higher hit rate (21.9%) than ascidians (7.1%). Using activity-directed purification, seven previously described compounds and four novel compounds, with varying activity against esophageal cancer cell lines, were isolated from the sponges Axinella weltneri, Aplysilla sulphurea, and Strongylodesma aliwaliensis. The results of this study suggest that subtidal benthic marine organisms collected off the coast of southern Africa hold potential for identifying possible drug leads for the development of agents with activity against esophageal cancer.

Cytotoxic pyrroloiminoquinones from four new species of South African latrunculid sponges.

An examination of organic extracts of four new species of South African latrunculid sponges, Tsitsikamma pedunculata, T. favus, Latrunculia bellae, and Strongylodesma algoaensis, yielded 13 known and eight new pyrroloiminoquinone alkaloids, 3-dihydro-7,8-dehydrodiscorhabdin C (4), 14-bromo-3-dihydro-7,8-dehydrodiscorhabdin C (5), discorhabdin V (6), 14-bromo-1-hydroxydiscorhabdin V (7), tsitsikammamine A N-18 oxime (10), tsitsikammamine B N-18 oxime (11), 1-methoxydiscorhabdin D (12), and 1-aminodiscorhabdin D (13). Standard spectroscopic methods provided the structures of the pyrroloiminoquinone metabolites, while chiral GC-MS analysis of the acylated ozonolysis products of 21 confirmed the stereochemistry of the l-histidine residue in this compound. The anticancer activity of 20 pyrroloiminoquinone compounds was explored in the HCT-116 cancer cell line screen, and the DNA intercalation of the tsitsikammamines, together with their ability to cleave DNA through topoisomerase I inhibition, is discussed.