Thesis (Ph. D.)--University of California, San Diego, 2009. / Title from first page of PDF file (viewed July 9, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 369-389).

Doctor of Philosophy / Department of Chemistry / Duy H. Hua / The first chapter in this thesis includes the design, synthesis, and evaluation of anti-Alzheimer and anti-norovirus activities of tricyclic pyrones (TPs). Alzheimer’s disease is a major cause of dementia and sixth leading cause of death; it is a growing problem all over the world. On the other hand, norovirus, a highly contagious agent is responsible for more than 90% of non-bacterial gastroenteritis causing severity mainly in the closed environments. No drugs exist to eradicate the symptoms developed by both of these disorders. Studies have shown that the development of Alzheimer’s disease and the infection of norovirus are dependent on cholesterol metabolism. More specifically, the inhibition of acyl-CoA: cholesterol acyltrasferase (ACAT) led to the reduction of plaques in Alzheimer’s disease as well as reduced the infection of norovirus. Mimicking the structure of CP2, a TP with promising anti-Alzheimer activities, a library of tricyclic pyrones containing phenyl, naphthyl, heterocyclic, and dipeptidyl moieties were synthesized and evaluated for their anti-Alzheimer and anti-norovirus efficacies. Several TPs containing phenyl and naphthyl groups showed sub-micromolar to nanomolar potencies for the protection of neuronal MC65 cells from Aβ-oligomers induced death. Similarly, the TPs containing pyrrolyl, imidazolyl, and quinolinyl moieties were effective to inhibit the norovirus replication in low micromolar range. The most effective TPs from MC65 cells protection assay were also effective in the inhibition ACAT and up-regulation ABCA1 gene. The second chapter in this thesis includes the design, synthesis, and anti-norovirus activity of thiouridine nucleosides. Many nucleosides have demonstrated effective inhibition of viral RNA polymerase, and some are progressing at different level of clinical trials for the treatment of hepatitis C virus. Some of the nucleosides, including 2’-C-methyl and 2’-amino substituted analogs, were found to effectively inhibit the norovirus replication. In the search of more potent anti-noroviral compounds, two thiouridine nucleosides were synthesized and evaluated as anti-norovirus agents. Both of these analogs were ineffective up to 50 μM for the inhibition of norovirus replication in cell based assay. Proposed work of converting these nucleosides to their phosphoramidate derivatives is also described.

BACKGROUND: Ethnobotanical knowledge continues to be important for treating illness in many rural communities, despite access to health care clinics and pharmaceuticals. However, access to health care clinics and other modern services can have an impact on the distribution of medical ethnobotanical knowledge. Many factors have been shown to be associated with distributions in this type of knowledge. The goal of the sub-analyses reported in this paper was to better understand the relationship between herbal remedy knowledge, and two such factors, age and social network position, among the Yucatec Maya in Tabi, Yucatan. METHODS: The sample consisted of 116 Yucatec Maya adults. Cultural consensus analysis was used to measure variation in herbal remedy knowledge using competence scores, which is a measure of participant agreement within a domain. Social network analysis was used to measure individual position within a network using in-degree scores, based on the number of people who asked an individual about herbal remedies. Surveys were used to capture relevant personal attributes, including age. RESULTS: Analysis revealed a significant positive correlation between age and the herbal medicine competence score for individuals 45 and under, and no relationship for individuals over 45. There was an insignificant relationship between in-degree and competence scores for individuals 50 and under and a significant positive correlation for those over 50. CONCLUSIONS: There are two possible mechanisms that could account for the differences between cohorts: 1) knowledge accumulation over time; and/or 2) the stunting of knowledge acquisition through delayed acquisition, competing treatment options, and changes in values. Primary ethnographic evidence suggests that both mechanisms may be at play in Tabi. Future studies using longitudinal or cross-site comparisons are necessary to determine the whether and how the second mechanism is influencing the different cohorts.

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Biological Sciences / Doctoral / Doctor of Philosophy

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No description available.

In this study, two plant species, Schefflera umbellifera (Araliaceae) and / Thesis (M.Sc.) - University of KwaZulu-Natal, Pietermaritzburg, 2007.

Cancer is a human tragedy that strikes and kills the lives of our beloved people. With a limited number of effective anticancer drugs from natural resources currently in use, there is a real need for new, safe, cheap and effective anticancer drugs to combat this dreaded and formidable disease. Plants have a long history of use in the treatment of cancer. Several plant-derived anticancer agents including taxol, vinblastine, vincristine, the camptothecin derivatives, topotecan and irinotecan and etoposide derived from epi- podophyllotoxin are in clinical use all over the world. In this study, two endemic plant species from the Rubiaceae and Asteraceae families, namely Anthospermum hispidulum E.Mey. ex Sond. and Eriocephalus tenuifolius DC. were investigated for their anticancer properties. The organic (methanol/dichloromethane, 1:1 v/v) extracts of both plant species were found to have moderate anticancer activity against a panel of three human cancer cell lines namely, breast MCF7, renal TK10 and melanoma UACC62 at the CSIR anticancer screen. Bioassay-guided fractionation of the organic extracts of Anthospermum hispidulum led to the isolation of an active compound which was characterised as ursolic acid. Another compound, namely scopoletin was also isolated. The compounds isolated here are known compounds, but have not previously been reported as present in the genus Anthospermum. Bioassay-guided fractionation of the organic extracts of Eriocephalus tenuifolius resulted in the isolation of 8-O-isobutanoylcumambrin B as the active constituent. This compound is reported to have been isolated from related plant species; however its biological activity is not known. The compounds pectolinagenin, hispidulin, friedelinol and tetracosanoic acid were also isolated, but did not show any significant anticancer activity. The structures of all compounds isolated in this study were elucidated using nuclear magnetic resonance spectroscopy, mass spectroscopy and also by comparison with data reported in the literature. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2008.