Marine biodiscovery from Floridian mangrove forests and Irish waters
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Natural products have been used since ancient times to treat illnesses and terrestrial organisms have been studied extensively from a chemical point of view. Marine organisms, on the other hand are definitely understudied compared to plants due to their difficult accessibility. However, technological advancements have made it possible for scientist to reach and sample from tropical waters to the deepest points of the world’s oceans. Ever since the discovery of spongouridine and spongothymidine, marine natural products have gained interest within the drug discovery community. The chemistry they produce has been shown beneficial for human health with many examples of marine-related compounds that made it into the market as potent drugs for severe diseases. This thesis is demonstrating the importance of marine microbes, corals and algae as a source of secondary metabolites and emphasis is also given on their biological activity. In particular, Chapter 2 is describing in detail the chemical investigation of an endophytic fungus isolated from a Floridian red-mangrove tree. As part of a high-throughput screening project which involved numerous fungal extracts that were screened against the ESKAPE pathogens, an Alternaria sp. isolate was chemically investigated. Bioassay-guided isolation of the fungal extract yielded a suite of new and known secondary metabolites which belong to the benzofuran (2.16-2.18) and benzopyrone (2.20) families and exhibited weak anti-MRSA activity. Part B of this thesis is focusing on the great unexplored potential of Irish Waters as source of new chemistry. Chapter 3 explores polyhalogenated monoterpenes produced by an Irish Plocamium cartilagineum sample. Six new and known linear and cyclic polyhalogenated monoterpenes were isolated and their structure elucidation process is thoroughly discussed. The cyclic polyhalogenated monoterpenes 3.2 and 3.3 have been previously described but this is the first report of crystal structure elucidation through X-ray analysis. The linear compounds 3.4 and 3.6 represent new polyhalogenated monoterpenes whereas compound 3.7 is a previously reported metabolite but full NMR data were not available until now. The new metabolite 3.4 exhibited significant cytotoxic activity when screened against cervical (HeLa) and pancreatic (MiaPaCa-2) cell lines. The next chapter, Chapter 4, investigates a deep-sea coral identified as Primona sp. which was collected in the Whittard canyon from various depths. A mixture of at least two ceramides (4.1) was isolated. Finally, Chapter 5 is focusing on the construction of a microbial library from Irish marine bacterial and fungal endosymbionts. One thousand seven hundred and fifty (1 750) endosymbiotic microbial strains were isolated from Irish algae, invertebrates and sediment samples. Priority was given to the fungal endosymbiotic isolates and each colony was cultured in a control treatment as well as in the presence of HDAC and DNMT inhibitors. More than fungal 1 200 extracts were screened against the ESKAPE pathogens and 10.8% of those showed antibacterial activity. The majority of the active extracts exhibited selective activity against only one of the ESKAPE pathogens. Interestingly, only 14 fungal cultures showed antimicrobial activity and for the majority of them only one treatment (control, HDAC or DNMT) was found active indicating that the each treatment should be treated as an independent sample/extract.
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