Browsing by Author "Sunassee, Suthananda N"
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- ItemOpen AccessCytotoxic activity of marine sponge extracts from the sub-Antarctic Islands and the Southern Ocean(2016) Olsen, Elisabeth K; de Cerf, Christopher K; Dziwornu, Godwin A; Puccinelli, Eleonora; Ansorge, Iabelle J; Samaai, Toufiek; Dingle, Laura M K; Edkins, Adrienne L; Sunassee, Suthananda NAbstractOver the past 50 years, marine invertebrates, especially sponges, have proven to be a valuable source of new and/or bioactive natural products that have the potential to be further developed as lead compounds for pharmaceutical applications. Although marine benthic invertebrate communities occurring off the coast of South Africa have been explored for their biomedicinal potential, the natural product investigation of marine sponges from the sub-Antarctic Islands in the Southern Ocean for the presence of bioactive secondary metabolites has been relatively unexplored thus far. We report here the results for the biological screening of both aqueous and organic extracts prepared from nine specimens of eight species of marine sponges, collected from around Marion Island and the Prince Edward Islands in the Southern Ocean, for their cytotoxic activity against three cancer cell lines. The results obtained through this multidisciplinary collaborative research effort by exclusively South African institutions has provided an exciting opportunity to discover cytotoxic compounds from sub-Antarctic sponges, whilst contributing to our understanding of the biodiversity and geographic distributions of these cold-water invertebrates. Therefore, we acknowledge here the various contributions of the diverse scientific disciplines that played a pivotal role in providing the necessary platform for the future natural products chemistry investigation of these marine sponges from the sub- Antarctic Islands and the Southern Ocean.
- ItemOpen AccessIdentification of Antimycobacterial Natural Products from a Library of Marine Invertebrate Extracts(2022-01-28) Acquah, Kojo Sekyi; Beukes, Denzil R; Seldon, Ronnett; Jordaan, Audrey; Sunassee, Suthananda N; Warner, Digby F; Gammon, David WTuberculosis (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 range
- ItemOpen AccessInvestigating the chemical diversity and biomedicinal potential of South African actinomycetes for tuberculosis drug discovery(2018) De Cerf, Christopher; Sunassee, Suthananda N; Meyers, Paul R; Warner, DigbyThe chemical diversity and biomedicinal potential of three South African actinomycetes, Streptomyces speibonae PK-BlueT , Streptomyces africanus CPJVR-H T and Streptomyces pharetrae CZA14T , was investigated. The primary aim was the isolation and structure elucidation of anti-tubercular natural products (NPs), including the re-isolation of the compound named PK-B, reported to be produced by S. speibonae PK-BlueT . Efforts were made to re-isolate the compound named PK-B. However, the results could not be replicated and focus was shifted to the bioassay-guided isolation of antimycobaterial compounds from the three actinobacteria. Culture conditions were optimised for antimycobacterial activity of S. speibonae PK-BlueT extracts by testing against the MTB analogue Mycobacterium aurum A+ (a non-pathogenic, fast-growing mycobacterium that has a similar antibiotic susceptibility to Mycobacterium tuberculosis). Bioactive crude extracts were prioritised for liquid-liquid partitioning and dereplication by LR LC-MS, followed by prefractionation and purification using a combination of HPLC and benchtop column chromatography. Structure elucidation of isolated compounds was achieved using NMR, LCMS and GC-MS data. Bioassays against M. aurum A+ were implemented at every stage of the isolation process to make sure that the isolated compounds had antimycobacterial activity. This strategy led to the isolation of four known compounds, the alkaloid N-phenylpyridin-2- aminium (3.1), a 1:1 mixture of the long-chain fatty acids (LCFAs) n-hexadecanoic acid (3.2) and 14-methylpentadecanoic acid (3.3), and the isoflavone 7-hydroxy-3-(4-hydroxyphenyl)- 4H-chromen-4-one (3.4), from S. speibonae PK-BlueT cultures. Of the four isolated compounds, only 3.1 has not previously been reported from a natural source. The approach of using M. aurum A+ in searching for anti-tubercular compounds was vindicated as 3.1, the mixture of 3.2 and 3.3, and 3.4, in addition to inhibiting the growth of M. aurum A+, exhibited activity against M. tuberculosis H37RvT with MIC90 values of 135 μM, 26 μM and 195 μM, respectively. Additionally, the effect of different growth media on the chemical diversity of S. speibonae PK-BlueT , S. africanus CPJVR-H T and S. pharetrae CZA14T extracts was demonstrated by bioassay where the extracts were screened against a panel of test organisms. HR LC-MS dereplication was used to identify a list of 11 suggested molecular formulae of potentially novel, bioactive NPs in liquid-liquid partitioned extracts of theses three filamentous actinobacteria. Unfortunately, these compounds could not be investigated further due to low biomass and time limitations.