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Posted on March 22, 2017
Date - March 22, 2017
Ph.D. Thesis Defense – 752
Title: Investigating the Chemical Diversity of Secondary Metabolites from Filamentous Fungi
Natural products continue to be a fertile source of leads for drug discovery as a large extent of the world’s biodiversity has been untapped for their chemical diversity and biological activity. With the continuing need for novel structures due to the increasing emergence of drug-resistant pathogens and diseases, natural products remain relevant to the future of drug discovery. Addressing this demand for unique structural diversity, my work has focused on identifying new leads from two ecological habitats including filamentous Ascomycetes from terrestrial and freshwater habitats. One of the major challenges of working with natural products is the re-isolation of known compounds. Thus, to address this issue, I worked to develop a method to dereplicate fungal cultures using a complementary suite of hyphenated techniques, specifically ultraperformance liquid chromatography-photodiode array-high resolution tandem mass spectrometry. This strategy allowed collection of mutually supportive data, such as chromatographic retention times, UV-VIS data, high-resolution mass spectrometric data, and mass fragmentation data (MS/MS) for targeted screening of compounds in our in house library. To take this method a step further, the identified hits were expanded upon by screening for potential analogues using mass defect filtering. This method being part of the dereplication strategy is important as it permitted re-evaluation of data when future compounds of interest are identified.