Electronic Theses and Dissertations

Date of Award

1-1-2011

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

Department

Biomolecular Sciences

First Advisor

Mark T. Hamann

Second Advisor

John S. Williamson

Third Advisor

Jordan Zjawiony

Relational Format

dissertation/thesis

Abstract

As part of our ongoing efforts to find new drug leads against infectious diseases, several terrestrial and marine macro- and microorganisms were investigated. Several bioactive molecules, presented below, were isolated from these natural products. The mass-screening of dozens of marine Actinomycetes was completed and several Streptomyces with interesting biological activity profiles identified. A few examples are the Streptomyces code H747 and the Streptomyces code H668, a bacterium from which a new (5) and two known polyethers, the antimalarial agent K41-A (6) and its C-29 analog (7) were isolated. Five new six-membered ring cyclic peroxides: plakinastreloic acid A (8), methyl plakinastreloate A (9), the C-12 epimers of methyl 13, 14-epoxyplakinastreloate (10 & 11), and plakinastreloic acid B (12) were isolated from a marine sponge of the genus Plakinastrella. Compounds 8 and 9 exhibited antifungal activities against Candida albicans (IC50 = 6.5 µg/mL and 3.5 µg/mL, respectively), Aspergillus fumigatus (IC50 = 4.0 µg/mL and 9.0 µg/mL, respectively) and Cryptococcus neoformans (IC50 = 4.0 µg/mL and 9.0 µg/mL, respectively). A moderate antimalarial activity against CQ-resistant and CQ-sensitive strains of Plasmodium falciparum was observed, as well. It was also established that 8 possesses anti-HCV (Hepatitis C Virus) activity. Two other compounds were isolated from HCV active methanol extracts of Inga fagifiolia (twigs) and Diplostephium rhodendroides (leaves). These compounds were identified as 2,3,4,5,6-pentahydroxy-2-(hydroxymethyl)hexanamide (14), the amide of a known molecule and 4,5-dihydroxy-3-[(3,4,5-trihydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy] pentanoic acid (15). The bioassay-guided approach used for their isolation and structure elucidation is reported here. The potential of scCO2 to inactivate bacteria trapped in the gut of oysters was studied. It was established that exposing oysters to CO2 at 100 bar and 37 °C for 30 minutes and at 172 bar and 60 °C for 60 minutes induced 2-log and 3-log reductions in the APC loads, respectively. The decrease in the microbial load as a result of treatment with scCO2 was found to be significant (P = 0.002). A blind study allowing sensory analysis of treated vs. untreated oysters was also completed; no significant difference in the physical appearance, smell, or texture was recorded.

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.