Date of Award
Ph.D. in Pharmaceutical Sciences
Stephen J Cutler
David E. Wedge
John M. Rimoldi
Both opioid and cannabinoid receptors belong to the large superfamily of GPCRs and play an important role in a variety of processes including pain, craving, neurodegeneration, metabolic regulation, anxiety and immune function. Therefore, recent advances and discoveries in opioid and cannabinoid receptors have paved the way for a very exciting future for opioid and cannabinoid receptors-based therapies to potentially treat a variety of conditions. However, the growing realizations of the complexity of these two receptors regulation in physiological and pathological conditions have discouraged the development of new therapeutics. So, it is important for us to identify new chemical scaffolds which act on opioid or cannabinoid receptors not only to probe these receptors in order to uncover the mystery of these two receptors but also to identify new leads for the development of new therapeutic agents. Natural products are substantially more diverse than combinatorial compounds and fungi-derived natural products are unexplored and untapped domains for opioid and cannabinoid receptors-based drug discovery. In addition, fungi have a very successful record in serving as sources of leads within the pharmaceutical industry. Therefore, it is reasonable and feasible to identify new agents from fungi which act on opioid or cannabinoid receptors. Radioligand binding assays for opioid and cannabinoid receptors have been a useful tool for the discovery of novel agents. With the use of this assay, four fungi species were selected and subjected to bioassay-guided fractionation affording a total of twenty-nine compounds which were identified using standard spectrometric and spectroscopic methods. Two new benzyl derivatives (1 and 2) and seven known compounds (3-9) were isolated and identified from the fungus Eurotium repens. Three new (10-12) and three known resorcylic acid lactones (13-15) were isolated from the fungus Neocosmospora sp. NRRL 22472. Three new (16-18) and ten known compounds (19-28) were isolated from the fungus Eupenicillium parvum. The research presented in this dissertation confirms the potential of fungi-derived natural products with binding affinities for opioid or cannabinoid receptors.
GAO, JIANGTAO, "Fungi-derived natural products with binding affinities for human opioid or cannabinoid receptors" (2010). Electronic Theses and Dissertations. 1446.
Emphasis: Medicinal Chemistry