O'Donnell, Gemma Louise;
(2007)
Phytochemical and Antimycobacterial Studies on the Liliales.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
The emergence of multi-drug resistant strains of many human pathogens, in particular those in the genera Mycobacterium and Staphylococcus, has led to an urgent need for the discovery and development of new antimicrobial agents. Mycobacterium species are the causative agents of tuberculosis (TB) and leprosy, while fast-growing species are responsible for chronic pulmonary and soft tissue infections. The resistance of Mycobacterium strains to front-line drugs has bought about a rise in cases of TB worldwide, particularly in association with the AIDS epidemic. Allicin, the principal constituent of Allium sativum (garlic), has been known as an antibacterial agent since the 1940's, and garlic was used as a treatment for TB in the early 19th Century. This project focuses on the antimycobacterial properties of the subterranean parts of lesser studied members of the Alliaceae and Liliaceae. Initial antibacterial screening of crude extracts, against strains of fast-growing Mycobacterium species, was carried out to assess possible leads. Extracts of chemical and antimycobacterial interest were then subjected to fractionation by a range of chromatographic techniques. Compounds were identified by 1D and 2D NMR techniques and verified with mass spectroscopy, IR, UV and polarimetry data. The antibacterial activity was assessed with a standard minimum inhibitory concentration (MIC) assay against fast-growing strains of mycobacteria. A number of the isolated natural products were also assessed for inhibition of the isocitrate lyase (ICL) enzyme, which has been shown to be an important factor in the persistence of tuberculosis. Inhibition was determined by a disc diffusion assay where the zone of inhibition was measured. During this study 28 compounds from a diverse range of chemical classes were isolated, and a number displayed moderate to good activity against the range of fast-growing Mycobacterium strains. Five new natural products were isolated; a homoisoflavanone (MIC; 16-256 μg/ml) and benzopyran (inactive) from Chlorophytum inornatum, and a dithio-pyridine-N-oxide (MIC; 0.5-1.0 μg/ml) from A. hollandicum and subsequently A. stipitatum with antimycobacterial activity comparable with current antibiotics and two fatty acids (MIC: 16-128 μg/ml). Cinnamaldehyde derivatives, in particular coniferylaldehyde, from A. neapolitanum displayed significant inhibition of the ICL enzyme.
Type: | Thesis (Doctoral) |
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Qualification: | Ph.D |
Title: | Phytochemical and Antimycobacterial Studies on the Liliales |
Open access status: | An open access version is available from UCL Discovery |
Language: | English |
Additional information: | Thesis digitised by ProQuest. |
Keywords: | Health and environmental sciences; Isocitrate lyase |
URI: | https://discovery.ucl.ac.uk/id/eprint/10105295 |
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