Steps in the journey to advance the study of nature’s chemistry
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Diana Kao (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- Nicholas Oberlies
Abstract: “A journey of a thousand miles begins with a single step” is a saying from the philosopher of Laozi, the founder of Taosim, and Taoism believes in living in harmony with the universe or nature itself. This seems particularly appropriate to describe the journey of this body of work, which itself is not beginning nor the end of the journey for research in natural products’ chemistry, which is to find new treatments by studying the nature herself. However, over the course of the past three decades, rational drug design and combinatorial chemistry have become major methods to develop pharmacologically significant drugs. Whereas, in the last 30 years, 64% of the approved small-molecule drugs originated from natural products, which studies nature’s building blocks. Classically, plants are the first image that comes to mind when one thinks of natural products when in fact, there is a wide diversity of sources such as microorganisms remain relatively unexplored. One such microorganism is fungi. Literature estimates there to be about 5 million fungal species and only 100,000 species having been identified-even fewer measured for their potential bioactivity. The way we think of natural products is changing, and so the way we work with natural products also needs to change. Presented here are the characterization of new and known compounds from a filamentous fungus (Aim 1), methods to augment the isolation techniques for a compound of interest from a fungal endophyte (Pencillium restrictum) for laboratory scale (Aim 2), and applying droplet probe, a unique in situ technique, to study natural products (Aim 3). Aim 1 was achieved through examining a filamentous fungus with very prominent cytotoxicity, which our group is interested in for anticancer activity. Macrocyclic trichothecenes, which are known to be complex and very cytotoxic, were isolated. However, many of these compounds were first identified in the early 1960s so absolute configuration was not available, but modern techniques were applied to solve and complete the literature for this class of compounds. Aim 2 was achieved two-fold through a media study to determine the best growing conditions for P. restrictum and then further optimizing the extraction, partitioning, and purification techniques compared to those previously published in literature. These techniques are important for compounds from fungi that have important biological activity because a large quantity of compound is necessary in order to conduct larger studies to get these potential drugs from the benchtop to the bedside. Aim 3 was achieved through the examination of a herbarium specimen of Garcinia mangostana with droplet probe. Although not a fungus, this plant produces prenylated xanthones, which are also known for their cytotoxic activities. This technique has been applied to fungi many times in our lab, and this is the first time a sample as delicate as a herbarium specimen has been examined. This method paves the way for the use of this technique for precious, older natural products that would have previously been permanently damaging during the analysis process.
Steps in the journey to advance the study of nature’s chemistry
PDF (Portable Document Format)
5301 KB
Created on 12/1/2019
Views: 247
Additional Information
- Publication
- Dissertation
- Language: English
- Date: 2019
- Keywords
- Droplet probe, Herbarium specimen, Macrocyclic trichothecene, Mangosteen, Natural products, Penicillium restrictum
- Subjects
- Natural products $x Biotechnology
- Botanical specimens
- Mangosteen
- Penicillium