Electronic Theses and Dissertations

Author

Xiaoning Wang

Date of Award

2012

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Stephen J. Cutler

Second Advisor

Christopher R. McCurdy

Third Advisor

John M. Rimoldi

Relational Format

dissertation/thesis

Abstract

Natural products have provided considerable value for drug discovery over the past half-century. Nearly four fifth of drugs were natural products or inspired by natural compounds. Bioactive secondary metabolites isolated from natural source, either fungal or terrestrial, are relatively safer for human health and the environment and can serve as drug or as drug leads for the development of synthetic or semi-synthetic analogs. Natural products have also been successfully used in agriculture as plant growth regulators, signal transductions, fungicides, herbicides and tranquilizers. In our continued efforts to identify bioactive compounds, seventy-seven plant and fungal extracts were evaluated using a direct-bioautography assay coupled with three Colletotrichum species to detect antifungal metabolites. Three crude extracts that shosignificant antifungal activity were selected for further bioassay-guided isolation. Various chromatographic techniques including preparative thin layer chromatography, vacuum liquid chromatography, flash chromatography, high pressure liquid chromatography and over pressure layer chromatography were utilized to isolate biologically active secondary metabolites from natural products of fungal and plant origin. Among all the techniques, over pressure layer chromatography were first adopt here for preparative isolation of natural products. It turned out to be a rapid and efficient method of exploiting co-migrating bioactive metabolites, and eleven compounds including two new molecules were isolated by using this technique. The structure of the isolated compounds was elucidated through various spectroscopic methods, including high-resolution mass spectrometry, one and two-dimensional nuclear magnetic resonance spectroscopy. Finally, the isolated compound was submitted for several in vitro assays, including antifungal, herbicidal, antibacterial, and cannabinoid and opioid receptor agonist assays. Some compounds shopotent antifungal activity against strawberry pathogens and one compound also shogood herbicidal and antibacterial activity. These compounds could be exploited as drug leads to potential agrochemicals or pharmaceuticals. All the promising drug leads have been submitted for antifungal testing using 24-well strawberry leaf disc assay.

Concentration/Emphasis

Pharmaceutics

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