Identification of glutathione S-transferase inhibiting natural products from Matricaria chamomilla and biotransformation studies on oxymatrine and harmine

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dc.contributor.supervisor Ata, Athar (Chemistry) en
dc.contributor.author Iverson, Chad
dc.date.accessioned 2010-09-10T22:22:11Z
dc.date.available 2010-09-10T22:22:11Z
dc.date.issued 2010-09-10T22:22:11Z
dc.identifier.uri http://hdl.handle.net/1993/4150
dc.description.abstract This thesis describes the results obtained from the phytochemical analysis of Matricaria chamomilla, and the microbial transformation of oxymatrine (85) and harmine (87), as summarized below. 1. Chemical investigation of the crude methanolic extract of Matricaria chamomilla resulted in the isolation of a new natural product, matriisobenzofuran (72), along with four known compounds: apigenin (73), apigenin-7-O-β-glucopyranoside (74), scopoletin (75), and fraxidin (76). The structures of compounds 72-76 were elucidated with the aid of extensive NMR and mass spectroscopic studies. All of the aforementioned compounds showed moderate to good inhibitory activities against glutathione S-transferase, an enzyme which has been implicated in the resistance of cancer cells to chemotherapeutic agents. These compounds were also evaluated for antioxidant activity and displayed moderate to good free radical scavenging activity. Additionally, compounds 72-76 were screened for anti-leishmanial activity. Compounds 75 and 76 were significantly active in this assay, while the remaining compounds were weakly active. In the antibacterial and antifungal assays, compounds 72-76 were not active. 2. The second part of this thesis deals with the biotransformation studies on oxymatrine (85) and harmine (87). Oxymatrine (85) was metabolized to the deoxy analogue, matrine (84) by Penicillum chrysogeneum (ATCC 9480), Cunninghamella bainieri (ATCC 9244), Cunninghamella blakesleena (ATCC 9245 and 8688A), Curvularia lunata (ATCC 12017), and Fusarium sp. In the time-based analysis of this transformation, the metabolism of oxymatrine (85) could be detected after 48 hours of incubation. Additionally, incubation of harmine (87) with Mucor plumbeus (ATCC 4740) resulted in the isolation of harmine-N-oxide (94). The biotransformed products (84 and 94) were identified using IR, UV, NMR, and mass spectroscopic techniques. Compound 94 was evaluated for its ability to inhibit the enzyme acetylcholinestrase, whose overexpression has been linked to Alzheimer’s disease, and was found to possess weaker activity than harmine (87). en
dc.format.extent 4828614 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Matricaria chamomilla en
dc.subject glutathione S-transferase en
dc.subject Alzheimer's disease en
dc.subject acetylcholinesterase en
dc.subject microbial transformations en
dc.subject oxymatrine en
dc.subject matrine en
dc.subject harmine en
dc.subject Leishmaniasis en
dc.subject NMR en
dc.title Identification of glutathione S-transferase inhibiting natural products from Matricaria chamomilla and biotransformation studies on oxymatrine and harmine en
dc.degree.discipline Chemistry en
dc.contributor.examiningcommittee Sorensen, John (Chemistry) Peeling, James (Pharmacology and Therapeutics) en
dc.degree.level Master of Science (M.Sc.) en
dc.description.note October 2010 en

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