Electronic Theses and Dissertations

Date of Award

2012

Document Type

Thesis

Degree Name

M.S. in Pharmaceutical Science

Department

Biomolecular Sciences

First Advisor

John Williamson

Second Advisor

Samir A. Ross

Third Advisor

Robert J. Doerksen

Relational Format

dissertation/thesis

Abstract

Leishmaniasis is a parasitic disease remaining a major public health problem. It causes illness and death especially in developing countries. Comchemotherapeutic agents currently used are often inadequate, requiring long courses of parenteral administration, having toxic side effects or becoming less effective due to the emergence of resistant strains. Thus, there is an urgent need for new, effective, and inexpensive drugs. In the fight against leishmaniasis, natural products are important sources of novel therapeutic agents. The goal of our research is to study secondary metabolites from endophytic fungi as a source of effective antileishmanial agents. Many crude extracts from endophytic fungi have been screened for antiparasitic activity against Leishmania donovani and Plasmodium falciparum. The active samples were further evaluated regarding their toxicity versus mammalian cell lines. From the results, DC401 was identified as a promising source of new antiparasitic compounds. Biotransformation is defined as the use of biological systems to modify substances that are not used for growth. The process leads to a modified chemical structure and therefore a change in activity of the biotransformed compound, if the activity and structure are correlated. The bioassay-guided fractionation of Limonium myrianthum resulted in the isolation of 5,7,2',4',5'- pentahydroxyflavonol. This compound possessed significant antifungal activity against the fungal pathogens Candida glabrata and Candida krusei at IC50 4.44 and 9.56 ?g/mL, respectively. Biotransformation of 5,7,2',4',5'- pentahydroxyflavonol compound was done in an attempt to improve its biological activity.

Concentration/Emphasis

Emphasis: Medicinal Chemistry

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