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Tan, Swee Ngin
Tan, Lik Tong
Mankind has historically utilised terrestrial sources in nature that enabled discovery efforts for novel natural products possessing unique biological activities to treat a variety of diseases. Owing to the increasing occurrences of drug-resistant pathogens and the decreasing rate of novel natural product discovery from terrestrial sources in recent years, there is a pressing need for quicker discovery of novel bioactive natural products.
Recognised as the largest ecosystem covering over 70% of the Earth’s surface in water, the oceans offer a remarkable chemical diversity of marine natural products with tremendous potential in drug discovery efforts. In the last five years, the use of in-tandem high resolution mass spectrometry (MS/MS) metabolomics approaches in drug discovery efforts have received considerable attention due to the profound improvements in dereplication and characterisation processes. With this in mind, three central objectives of this research have been described: 1. To access the potential of various Singapore marine cyanobacterial collections in drug discovery efforts, 2. To evaluate the performance of an in-tandem mass spectrometry (MS/MS)-based metabolomic approach in the detection of marine natural products, 3. To validate the use of in-tandem mass spectrometry (MS/MS)-based metabolomic approaches integrated in drug discovery efforts. The aplysiatoxins are known toxic compounds detected in the proposed MS/MS–based metabolomic approach. Subsequent work in this research provided insights to the biomedical potential of aplysiatoxins as quorum sensing inhibitors. Two new compounds, benderamide A and trikopeptin, were isolated that also involved metabolomic approaches. Both compounds are cyclic depsipeptides, with benderamide A and trikopeptin showing brine shrimp toxicity and quorum sensing inhibition, respectively.
Based on the results obtained in this research, it is expected for the oceans to play an instrumental role in continuing mankind’s pursuit to treat diseases in the future.
|Appears in Collections:||Doctor of Philosophy (Ph.D.)|
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