Structural and synthetic investigations of South African marine natural products

A chemical investigation of six different marine invertebrates, collected along the South African coastline, resulted in the isolation and structural elucidation of fifteen previously undescribed secondary metabolites along with seven known compounds. The structures of the new metabolites were determined by a combination of spectroscopic and chemical methods. The endemic false limpet Siphonaria capensis was shown to contain two unusual polypropionate metabolites capensinone (162) and capensifuranone (163) as well as 2,4,6,8-tetramethyl-2-undecenoic acid (164) and the known polypropionates (E)- and (Z)siphonarienfuranone (149 and 161). Capensinone is the first example of a marine polypropionate containing a cyc1opentenone moiety. An investigation of the endemic South African soft coral Pieterfaurea unilobata yielded six new, highly oxygenated, pregnadiene sterols (180-185) and the known metabolite (169). Compounds 180-185 are the first pregnadienes obtained from the marine environment containing a C-7 substituent. An alternative procedure for the quick assignment of the absolute configuration at C-3 in this series of compounds was proposed. A companson of the pyrroloiminoquinone alkaloids of three undescribed l'}trunculid sponges resulted in the isolation of 3-dih¥drodiscorhabdin C (243), 3-dihydrodiscorhabdin B (244), discorhabdin H (197) and the previously reported alkaloids discorhabdin A (189) and discorhabdin D (192). While all three sponges were found to be morphologically different they all contained discorhabdin A as the major metabolite and discorhabdin H as one of their minor metabolites. It was found that a feature common to most of the South African latrunculid sponges is the reduction of the C-3 carbonyl gr,o up in some of the minor metabolites. The indole alkaloids, dilemmaones A-C (261-263), containing an unusual cyc1opentanone-indole skeleton, were isolated in trace amounts by bioassay guided fractionation of an extract obtained from a mixed collection of sponges collected near Cape Town. In an attempt to acquire more of these novel compounds for further investigation of their biological activity, several synthetic strategies towards their total synthesis were explored. A key feature of these approaches was the exploitation of the regioselective Gassman's artha-alkylation procedure for the introduction of an aromatic methyl substituent

Ten years of marine natural products research at Rhodes University

Marine invertebrates, algae and microorganisms produce a plethora of structurally unique and biologically active secondary metabolites. The ecological roles of these natural products, although not completely understood, range from chemical defence against predation to intra-specific cues for larval settlement. Surprisingly, a number of these metabolites have also shown potential as new medicines for the treatment of a variety of diseases including cancer. The natural products chemistry of southern Africa’s unique marine flora and fauna is relatively unknown and this review provides an overview of the contribution made by the marine natural products research group at Rhodes University to the isolation, identification and synthesis of biologically active natural products from southern African marine microorganisms, algae, sponges, ascidians, soft corals and molluscs

Tandem lc-ms identification of antitubercular compounds in zones of growth inhibition produced by South African filamentous actinobacteria

Novel antitubercular compounds are urgently needed to combat drug-resistant Mycobacterium tuberculosis (Mtb). Filamentous actinobacteria have historically been an excellent source of antitubercular drugs. Despite this, drug discovery from these microorganisms has fallen out of favour due to the continual rediscovery of known compounds. To increase the chance of discovering novel antibiotics, biodiverse and rare strains should be prioritised. Subsequently, active samples need to be dereplicated as early as possible to focus efforts on truly novel compounds. In this study, 42 South African filamentous actinobacteria were screened for antimycobacterial activity using the agar overlay method against the Mtb indicator Mycolicibacterium aurum under six different nutrient growth conditions. Known compounds were subsequently identified through extraction and high-resolution mass spectrometric analysis of the zones of growth inhibition produced by active strains. This allowed the dereplication of 15 hits from six strains that were found to be producing puromycin, actinomycin D and valinomycin

Antibacterial Activities of Selected Green Seaweeds from West African Coast

The continually increasing antibiotic resistance amongst microorganisms had steered up an increased intensity in the search for new drugs. The marine environment had been reported to be a great source of novel compounds with diverse biological activities and this had engendered the attention of researcher globally, but the West African Coast despite being blessed with a variety of Macro-algae remain untapped. This study was, therefore, embarked upon to investigate the antibacterial activities of selected green algal species from the West African coast. Crude extracts of Ulva fasciata, Ulva lactuca, Chladophora vagabunda, Caulepa taxifolia, Chaetomorpha antennina and Chaetomorpha linum were obtained by maceration using Dichloromethane/methanol (DCM/MeOH), chloroform/methanol (CHL/MeOH) 90% (v/v), Ethanol and Diethyl ether as solvents. Extracts were screened against some bacterial pathogens including Gram-positive bacteria- clinical strain (Sa I), S. aureus laboratory strain (Sa II), S. aureus ATCC 25922 (Sa III), Bacillus subtilis (Bs), Streptococcus pneumonia (Sp), Streptococcus faecalis (Sf) and Mycobacterium aurum (Ma). Gram-negative test bacteria were Escherichia coli clinical (Ec I) and Escherichia coli laboratory strain (Ec II), Escherichia coli NCTC 10418 (Ec III), E. coli ATCC 25923 (Ec IV), Proteus vulgaris (Pv), Proteus mirabilis (Pm), Pseudomonas aeruginosa (Pa) Pseudomonas putida (Pp), Salmonella typhi clinical strain (St I), Salmonella typhi NCTC 8385 (St II), Serratia macerans (Sm) and Klebsiella pneumonia (Kp). Crude extracts were obtained using Antibacterial screening was carried out by disc diffusion method. The result analysis was done by mean ± SD. The result showed that all the screened algae had antibacterial activity against at least one of the test organisms. Four (57%) of the seven algal species tested demonstrated inhibitory activities against the Gram-positive test bacteria while all the seven species tested showed inhibitory activities against the Gram-negative test bacteria. Highest inhibitory zone against Gram-negative bacterial species was observed in dichloromethane/methanol extract of Caulepa taxifolia (DCCT) against E. coli measuring 14.67 mm while the highest activity against Gram-positive bacterial strain was observed in diethyl acetate extract of Chaetomorpha antennina (DECA) against S. aureus (SaII) with an inhibitory zone of 17.67 mm. Extracts of Chaetomorpha antennina showed the highest inhibitory activities in this study. The result of this study showed that extracts from species of green macro-algae from the West African Coast possess antibacterial compounds that can serve as lead drug candidates in the quest for new antibacterial therapy if well explored

Hyphenated LC-ICP-MS/ESI-MS identification of halogenated metabolites in South African marine ascidian extracts

Extracts of 13 species of marine ascidian collected in Algoa Bay were analyzed by LC-ICP-MS/ESI-MS. This technique allows parallel analysis of the molecular species and the presence of certain elements. The LC-ICP-MS/ESI-MS technique was used to target iodinated metabolites in this study. Three ascidian species afforded the known 3,5–diiodo-4-methoxyphenethylamine (12), which was confirmedby the isolation of this metabolite fromAplidium monile.MS also suggested the presence of theknown 3,5–dibromo-4-methoxyphenethylamine (10) and the new 3-bromo-5–iodo-4-methoxyphenethylamine (11) in the A. monile extract. The presence of the known 3,5-dibromotetramethyltyrosine (21) and the new 3-iodotetramethyltyrosine (23) in extracts of an unidentified Didemnum species was similarly proposed from MS evidence. This is the first report of the occurrence of iodinated metabolites in South African marine invertebrates.IS

Semi-synthesis and evaluation of sargahydroquinoic acid derivatives as potential antimalarial agents:

Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against a chloroquinone sensitive strain of Plasmodium falciparum (D10). In this study we explored the antiplasmodial activity of several semi-synthetic analogs of sargahydroquinoic acid

Identification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts

Tuberculosis (TB) remains a public health crisis, requiring the urgent identification of new anti-mycobacterial drugs. We screened several organic and aqueous marine invertebrate extracts for their in vitro inhibitory activity against the causative organism, Mycobacterium tuberculosis. Here, we report the results obtained for 54 marine invertebrate extracts. The chemical components of two of the extracts were dereplicated, using 1H NMR and HR-LCMS with GNPS molecular networking, and these extracts were further subjected to an activity-guided isolation process to purify the bioactive components. Hyrtios reticulatus yielded heteronemin 1 and Jaspis splendens was found to produce the bengamide class of compounds, of which bengamides P 2 and Q 3 were isolated, while a new derivative, bengamide S 5, was putatively identified and its structure predicted, based on the similarity of its MS/MS fragmentation pattern to those of other bengamides. The isolated bioactive metabolites and semi-pure fractions exhibited M. tuberculosis growth inhibitory activity, in the rang

Halogenated oxindole and indoles from the South African marine ascidian Distaplia skoogi:

The known 3,6-dibromoindole (1), 6-bromo-3-chloroindole (2) and 6-bromo-2-oxindole (3) were isolated from the marine ascidian (sea squirt) Distapia skoogi collected from Algoa Bay, South Africa. Standard spectroscopic techniques were used to elucidate the structures of 1-3. All three compounds were found to be moderately cytotoxic to metastatic MDA-MB-231 breast cancer cells

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

The 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