Combining biological and chemical approaches in marine biodiscovery
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Marine organisms are prolific producers of novel and structurally interesting metabolites. The identification of marine natural products contributes to many scientific areas including pharmacology, chemical ecology, chemical synthesis, and others. Today various methodologies are used to select marine organisms that potentially contain bioactive metabolites. In this thesis we used two different strategies to select promising marine organisms. The first strategy is the High Throughput Screening (HTS) of Irish marine organisms’ extracts against a cancer related target. With that purpose a library of 916 marine organisms’ extracts was composed, a colorectal cancer cell line resistant towards 5-fluorouracil was prepared and the HTS of the library was conducted on this target. Through this strategy, only one known structure was elucidated among the ‘hits’. Therefore, another methodology directed towards the construction of a marine chemical library was employed which was based on a selection of marine organisms using their taxonomy. The chemical investigation of species of the genus Haliclona yielded two new and six known compounds. Next, the taxonomy based selection was improved by addition of HPLC-DAD-ELSD chemical screening. The chemical screening of 27 sponges belonging to the order Haplosclerida from the Caribbean and Poecilosclerida order from Ireland, led to the selection of two sponges: Clathria strepsitoxa and Siphonodictyon coralliphagum. In total of 12 new compounds were isolated including interesting sesquiterpene (hydro)quinones together with four known compounds. In total, eight marine organisms were chemically investigated which led to the characterization of 14 new metabolites and 11 known. Methodologies towards selection of promising marine organisms for drug discovery are discussed.
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