This thesis details my investigations of marine cyanobacterial natural products that resulted in the discovery of eighteen new secondary metabolites. Isolation and characterization of these unique molecules were carried out using different chromatographic techniques and by careful analyses of 1D and 2D NMR data, respectively. Preliminary bioassays of the crude...
The isoprenoid pathway is one of the major biosynthetic pathways of secondary metabolites. Isoprenoids with a C₂₀ skeleton are known as diterpenoids and are derived from the common precursor, geranylgeranyl diphosphate (GGPP). This dissertation describes approaches to discover the diterpene synthase enzymes which provide the backbone structures for pleuromutilin and...
This thesis details my investigation of some pharmaceuticals and natural products on the transport of drugs which are substrates of P-glycoprotein (P-gp), such as cyclosporin A (CSA) and digoxin by using Caco-2 and MDCKII-MDR1 drug transport models. Three objectives were performed to address this goal. The first objective was to...
Male Sprague Dawley rats received a single intraperitoneal dose
of BCNU in experiments designed to measure biochemical changes associated with the pulmonary toxicity described for this agent. Changes in
serum and lung lavage angiotensin converting enzyme (ACE) activity
were measured to detect changes in pulmonary endothelial cell integrity. Alpha-1-proteinase inhibitor...
Microbial natural products represent a massive repository of unique chemical scaffolds with corresponding diverse biological functions. However, in the past decade the development of natural products into new therapeutics has dwindled, in part due to the challenges posed by high rediscovery rates and low throughput associated with classical bioassay-guided fractionation...
Metagenomics has revealed that the marine microbial biosphere is immensely more diverse than originally considered, and is an almost untapped reservoir for the potential discovery of microbial natural products. Despite numerous advances in culturing, biosynthetic engineering and genomic-based screening efforts to uncover much of this diversity in relatively accessible environments,...