Electronic Theses and Dissertations

Date of Award

1-1-2010

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Biomolecular Sciences

First Advisor

Stephen J Cutler

Second Advisor

David E. Wedge

Third Advisor

John M. Rimoldi

Relational Format

dissertation/thesis

Abstract

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.

Concentration/Emphasis

Emphasis: Medicinal Chemistry

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.