Search

Colour is a remarkable feature among animals and it has diverse roles including camouflage, signalling, and photoprotection, all of which impact survival and reproduction. Moreover, colour is not always a fixed feature and can vary within a species, either between individuals or throughout an individual’s life, and is generated by nanostructures and/or pigments. Animal pigments can be synthesised or acquired through diet, with common pigment classes including carotenoids, tetrapyrroles and melanins. Research on pigments has gained momentum due to their numerous scientific and industrial applications. For instance, the green fluorescent protein (GFP), a fluorescent marker first identified in the jellyfish Aequorea victoria, is widely used in biomedical research. Despite the intense scientific interest in GFPs, little is known about the phylogenetic distribution and function of jellyfish pigments. Catostylus mosaicus, for instance, a rhizostome jellyfish that occurs abundantly in eastern Australia, can exhibit striking colour variation: it can be blue, white, or brown, and may also feature a blue band around the bell and/or oral arm proximal margins. However, the pigments responsible for these colours and the underlying drivers of colour variation are unknown. Therefore, the main objective of this thesis was to integrate chemical and genetic analyses to investigate colour variation in Catostylus mosaicus. [...], Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Environment and Sc, Science, Environment, Engineering and Technology, Full Text

Full Text, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Pharmacy & Med Sci, Griffith Health, Echium plantagineum L. (Boraginaceae) is an annual or biennial flowering plant native to the Mediterranean region, including western and southern Europe, northern Africa, and southwestern Asia. It was introduced to Australia as an ornamental plant in the 1800s and is commonly known as Paterson's curse or Salvation Jane. Due to its adaptive ability, it has become one of Australia's most costly, noxious, and invasive weeds. It has spread widely in the eastern and south-eastern states of Australia where it is estimated to have influenced 30 million hectares of agricultural land. However, to date, there is limited natural products research related to phytochemical and biological screening of compounds isolated from E. plantagineum. This thesis outlines a comprehensive chemical investigation and subsequent in vitro cytotoxicity screening of E. plantagineum to investigate a possible medicinal use for this invasive weed (Chapter 2 to Chapter 6). To achieve this, E. plantagineum was firstly collected from farmland in Mulwala, and Young, NSW, Australia. Each plant was then separated into different parts, including leaf, flower, root, and stem, and extracted with methanol to obtain eight crude extracts. The first goal of the project was to isolate, purify and identify secondary metabolites direct from chemical profiling employing mass spectrometry. Chapter 2 describes the isolation and preliminary chemical screening of E. plantagineum methanolic extracts of each part. The chemical fingerprint of E. plantagineum methanolic extracts was conducted by LC-MS in both positive and negative modes to identify and predict different classes of compounds. Previous phytochemicals reported include pyrrolizidine alkaloids, naphthoquinones and flavonoids. Our chemical predication also indicated an abundance of polyphenols such as rosmarinic acid, globoidnan A and rabdosiin among other derivatives. Chapter 3 and 4 report the identification and structure elucidation of secondary metabolites is

Full Text, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Environment and Sc, Science, Environment, Engineering and Technology, This thesis covers a wide range of research on marine natural products with a focus on their role in drug discovery. Chapter 1 starts with a general introduction to marine natural product chemistry, describing current trends and problems. It gives an insight into the importance of the discovery of new antibiotics in this pressing time where multidrug-resistant bacteria are on the rise. Chapter 2 is a meta-analysis of current trends in marine microbial natural product research and an analysis of how much of their chemistry overlaps with the chemistry of terrestrial microbial natural products. Over the past decade, research has greatly shifted to focus on marine microbial natural products, at the expense of marine macro-organism studies. An assessment of the structural overlap between 55,817 published marine and terrestrial microbe and marine macroorganism natural products, using structural fingerprints and scaffold clustering, was enlightening. The results showed that currently 76.7% of the chemistry found in marine microbes is vastly similar to the chemistry isolated from terrestrial microbes. This overlap is mainly due to the use of terrestrial isolation and culturing methods that select for the growth of terrestrial-like bacteria instead of unique marine bacteria. As a result, the unique chemistry associated with truly marine microbe species that are in close symbiotic relationships with marine macro-organisms is being missed. Chapter 3 describes the antimicrobial assay development and screening of a large collection of Australian marine invertebrate specimens for activity against four different strains of bacteria. It resulted in 12.5% of all the specimens tested, showing activity against the drugresistant strain of Staphylococcus aureus (MRSA) but lower bioactivity rates against Pseudomonas aeruginosa (0.76%) and Escherichia coli (0.76%). This illustrates how much harder it is to find activity against Gram-negative bacteria such as P. aeruginosa and E. coli. To

Tribe Eucalypteae, commonly known as the Australian eucalypts, is an economical, pharmacological, chemically, and historically important group consisting of over 850 species. These angiosperms are the number one source of hardwood globally with over 200,000 km2 of plantation dedicated to E. globulus. E. grandis and E. robusta, they possess cultural and ethnomedicinal significance, rooted deep in the heritage and culture of the Australian indigenous populations and have acted as sources of biologically active new small molecules in the modern era. The relationship between these plants has been the source of scientific debate and intrigue since the early 1900s, coming to a head in 1995 when the genera Angophora and Corymbia were delineated from the large genus Eucalyptus. The rearrangement of the relative taxonomic rank of these taxa sparked intensive research into the Australian eucalypts, with 86.7 % of the 36,264 publications containing Eucalyptus, Corymbia and Angophora being published since the 1995 taxonomic revision. Despite this large quantity of research, the delineation of these genera remains blurred due to morphological similarities, and ambiguous results from chemotaxonomic studies. Due to this, we have performed the largest chemical investigation of tribe Eucalypteae to date, utilizing a mixture of traditional natural product isolation and discovery methodologies accompanied by modern chemoinformatic analysis, statistical and machine learning investigation of the NMR assignments of published formyl phloroglucinol and [beta]-triketones, and the novel application of non-uniformly sampled HMBC as a chemotaxonomic probe to qualitatively identify the presence of key moieties of chemotaxonomic significance. [...], Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Environment and Sc, Science, Environment, Engineering and Technology, Full Text

Natural compounds have been commercially used in pharmaceutical industry due to their therapeutic nature. Herein, natural compounds are screened that modulate various biological processes that are known to be conserved from yeast to human and to be associated with human diseases such as cancers and viral infections. Baker’s yeast Saccharomyces cerevisiae is a eukaryotic model in the pharmaceutical industry and its use allows genome-wide recognition of potential targets of natural compounds. Cancer is one of the leading causes of death worldwide with the number of diagnosed cases of this disease escalating. Chemotherapy remains the number one treatment option, especially in developing countries where other forms of treatment remain costly. The anthracyclines (natural compounds) are chemotherapeutic agents that have been in use for the last forty years and that are effective in treating various solid tumours as well as haematological malignancies. Various modes of action have been suggested for these agents; however, it remains unclear as to how these agents really exert their cytotoxic effects on cells. Anthracyclines can cause severe adverse effects such as cardiotoxicity as well as myelosuppression, and these are the major limitations of these drugs. To solve these problems, the controversy regarding their mechanism of action needs to be addressed. For this reason, here the focus is on the analysis of molecular mechanisms responsible for anthracycline cytotoxicity and the identity of the intracellular compartments that anthracyclines localise to in a mammalian cell line and relate the findings to those controversies found in the literature. In addition, natural compound-based potential anti-viral compounds that may inhibit cellular vacuolar protein sorting-4 (Vps4p) ATPase activity and in parallel block viral budding from the cellular membrane were also investigated. Natural compounds have been largely excluded from characterisation via high-throughput profiling st, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Pharmacy & Med Sci, Griffith Health, Full Text

Marine natural products biodiscovery continues to evolve into an increasingly more sophisticated and multidisciplinary field. Since the first reported marine compound in the 1970’s, there have been more than 33,000 marine natural products reported in the literature with seventeen marine-derived drugs currently approved for therapeutic use worldwide. Despite this, how much do we really know about marine natural product chemical space with respect to biological activity, and are we examining these precious resources against suitable disease targets that aim to maximise their potentials for drug discovery? Currently, most marine drugs are approved for the treatment of cancer, however, because most marine natural products are inactive in these assays, should this continue to be the main emphasis for exploration of their potential bioactivity? Instead, should we be placing a larger emphasis on leveraging these precious natural resources against more suitable disease and infection targets? This thesis attempts to answer the aforementioned questions using multidisciplinary approaches toward marine natural products biodiscovery that aim to maximise the bioactivity ascribed to marine derived and/or inspired compounds for drug discovery. The introduction to the thesis presented in Chapter 1.0 provides an informative overview focused on the history of marine natural products and their roles in modern drug discovery and development. Chapter 2.0 explores a meta-analysis of the biological activities reported for marine indole alkaloids, a diverse and increasing sub-class of marine natural products represented across most marine phyla. Our analyses found that the biological potentials for 85% of marine indole alkaloid chemical space is unexplored or undefined. Further, most marine indoles are continuing to be examined for cytotoxicity and antimicrobial activities despite the fact that they are unlikely to display meaningful activities in these assays. Using cheminformatics analyse, Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Environment and Sc, Full Text

The Winteraceae are a small primitive family of angiosperms endemic to the cool rainforests and montane subtropics of South America, Melanesia, Australasia, and South-East Asia below the Wallace line.The medicinal value of Winteraceae plants branches from extensive use in traditional medicine regimens to use in modern clinical applications. Nonvolatile drimane sesquiterpenes do not occur broadly in nature. However, they are reported to be a chemotaxonomic characteristic of the Winteraceae. Many of those identified from the Winteraceae comprise structural features that are either unique to the family or identified from a minimal number of natural sources.3 Biological investigations on the drimane structure class have identified several activities attractive for drug discovery and may be linked to their usefulness in traditional medicines. Bubbia and Tasmannia are the only Winteraceae genera with species endemic to Australia. Except for Tasmannia lanceolata and studies on the essential oil content of both genera, the chemistry of the Australian Winteraceae is poorly studied and remains an unexploited source of potentially new biologically active natural products.The primary aim of this thesis was to investigate the chemistry of unexplored Australian Winteraceae species to identify new drimane sesquiterpene natural products and improve the current knowledge of the chemistry of Australian Winteraceae. This was achieved by exploring the chemistry of two Australian Winteraceae species., Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Environment and Sc, Science, Environment, Engineering and Technology, Full Text