- Title
- Studies in marine natural products: 1. dynamin 1 screening of sponges from Catherine Hill Bay 2. chemistry of Cystophora xiphocarpa 3. investigation of “paua greening” of Haliotis iris from New Zealand’s Cook Strait
- Creator
- Mhd Bakri, Yuhanis
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2015
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Crudely partitioned extracts of nine sponge samples from Catherine Hill Bay, NSW, Australia, were screened for dynamin 1 bioactivity. Dynamin 1 is an enzyme that is essential for clathrin coated vesicle formation in endocytosis and has been linked to many neurological disease for example amyotrophic lateral sclerosis (ALS) and Alzheimer. At 1 mg / mL, the methanol extract of sponge YMB080612CB01 showed the strongest inhibition, i.e. lowest dynamin 1 activity (5%), among all tested samples. Bioassay-guided isolation of these extracted fractions to yield pure active compounds was to no avail, as activities were lost during fractionation and compounds targeted because of the appearance of distinctive ¹H NMR signals (not lipids or steroids) continually disappeared. Fucosterol (76) was isolated from an inactive fraction. In a separate study, chemistry of endemic Australian brown alga Cystophora xiphocarpa was investigated. Steroidal compounds that had been previously isolated from C. xiphocarpa were re-isolated using a more efficient methodology. These compounds, comprising nine steroids (76 to 84) and a phaeophytin 86 were screened for antibacterial, anticancer and dynamin 1 bioactivity. All tested compounds revealed no antibacterial activity against S. epidermis, E. faecalis and M. catarrhalis. Of the compounds tested against 12 cancer cell lines, steroid 83 displayed GI₅₀ 8.7 ± 0.7 µM in colon cancer line HT29, GI₅₀ 5.6 ± 0.8 µM in breast cancer line MCF-7 and GI₅₀ 4.5 ± 0.2 µM in ovarian cancer cell line A2780 which makes it the most active anticancer tested compound in this steroid series. Steroid 78 is active against the ovarian cancer cell line A2780 with GI₅₀ 6.2 ± 0.1 µM, the colon cancer cell line HT29 with GI₅₀ 18 ± 0.0 µM and the breast cancer cell line MCF-7 with GI₅₀ 21 ± 6.00 µM, while its epimer, steroid 77, is inactive against all cell cancer lines. Diastereoisomers 81 and 82 showed moderate activities against dynamin 1 with IC₅₀62.9 ± 15.2µM, the first reported potential dynamin 1 inhibitor from natural sources. Phaeophytin A 86, which has been suggested to have potential for treating neurodegenerative diseases was found to be inactive in dynamin 1 screening. Investigation of the configuration of diastereoisomers of steroids 77 and 78 was completed by derivatization of compound 78 using phosgene to form a cyclic carbonate 108, molecular modelling and coupling constant analysis. In addition, compounds previously not reported from C. xiphocarpa were isolated. These compounds are a series of steroids (87 to 92, 98) and fucoxanthin (99). Compounds 88 to 90 displayed no potential anticancer activities against all cancer cell lines. Fucoxanthin, which was tested for antibacterial activity, is inactive. In the third study, abalone Haliotis iris which displayed “paua greening” was investigated. The greening of abalone meat which occurs when the abalone is prepared for market causes the meat to be downgraded and consequent commercial loss. Samples collected from Victory Island, New Zealand, were studied in comparison to control samples which were collected from Cook Strait, New Zealand. Through comparative analysis it was revealed that paua greening sample has different chemical composition in comparison to control sample.
- Subject
- marine natural products; steroids; algae; abalone; dynamin
- Identifier
- http://hdl.handle.net/1959.13/1295874
- Identifier
- uon:19142
- Rights
- Copyright 2015 Yuhanis Mhd Bakri
- Language
- eng
- Full Text
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| View Details Download | ATTACHMENT02 | Thesis | 14 MB | Adobe Acrobat PDF | View Details Download |