Our quest for pharmaceutically important marine natural products led to re-isolation of known mandelalides A-D and identification of new congeners E-L from re-collected South African Lissoclinum tunicate specimens. Mandelalides A, B, and L were characterized as selective cancer cell toxins, with an unusual activity profile influenced by their glycosylation /...
The numerous different types of nanomaterials and paucity of reliable in vivo information on toxicity has resulted in enduring uncertainties associated with health and safety risks, thereby slowing progress in nanotherapeutic assessment and development. This dissertation explores how the embryonic zebrafish model can be applied to prioritize commonly used nanomaterial...
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,...
Histone deacetylase (HDAC) inhibitors have the potential to de-repress epigenetically silenced genes in cancer cells, leading to cell cycle arrest and apoptosis. Dietary HDAC inhibitors derived from natural phytochemicals are promising anticancer agents. In this thesis, metabolites from natural organosulfur and organoselenium compounds, i.e. allyl mercaptan (AM), β-methylselenopyruvate (MSP) and...
Met is a prognostic indicator of colorectal cancer patient survival. Therapies that target Met may therefore have beneficial outcomes in the clinic. Recently, EGCG was reported to suppress Met activation, although the mechanisms were not elucidated. HCT116 and HT29 human colon cancer cells were used to examine the relationships between...
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...
Targeting the epigenome, including the use of histone deacetylase (HDAC) inhibitors, is a novel strategy for cancer chemoprevention. Sulforaphane (SFN), a compound found at high levels in broccoli and broccoli sprouts, is a potent inducer of Phase 2 detoxification enzymes and inhibits tumorigenesis in animal models. SFN also has a...
The antimutagenic potency of wheat grain and berry extracts was studied in vitro against several heterocyclic amines (HCAs) using the Salmonella mutagenicity assay and the anticarcinogencity of wheat grain was studied in vivo using the rat colonic aberrant crypt focus assay. Wheat bran, which binds HCAs in vitro, as well...