Date of Degree

5-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biology

Advisor

Ana Vallor

Advisor

Christopher Pierce

Advisor

Paulo Carvalho

Abstract

Schistosomiasis is a neglected tropical disease rampant in developing countries. Widespread chemotherapy is reliant on a single drug, praziquantel, which increases the risk of resistance and creates an urgent need for the development of new alternatives for treatment. Fungal biotransformation is a well-documented tool in the pharmaceutical synthesis of new drugs. This study examined the efficacy of four fungal strains, Cunninghamella elegans (ATCC 9245 and ATCC 8688a), Umbelopsis ramanniana, (ATCC 9628) and Yarrowia lipolytica (ATCC 20225), in the biotransformation of praziquantel. Colonies were cultured, dosed with praziquantel, incubated for 5, 10 or 15 days to metabolize, after which the cultures were filtered, metabolites extracted and subjected to HPLC analysis. Once the optimal time for metabolization was ascertained cultures were exposed to variable drug doses, either single or double. C. elegans, ATCC 8688a, fully metabolizes praziquantel after 15 days producing major peaks at 4.7 and 4.3 minutes; and responded more efficiently to a double dose. After 15 days C. elegans, ATCC 9245, had metabolized the majority of praziquantel producing major peaks at 4.7 and 4.3 minutes, and was equally efficient with an increased dose. U. ramanniana, fully metabolizes praziquantel after 10 days producing major peaks at 4.9 and 4.5 minutes, however, failed to produce metabolites with increased dosage. Y. lipolytica, showed negligible metabolic activity. The praziquantel peak remained relatively unchanged at 8.1 minutes for each time course and was not exposed to variable doses. Purification of the mixture and further testing is required to identify the metabolites obtained.

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