| || || Prasad, Pritesh.|
| || || Extraction, isolation, purification and characterization of bioactive compounds from the marine sponge Melophlus sp. |
Institution: University of the South Pacific.
Subject: Marine metabolites -- Solomon Islands , Sponges -- Microbiology -- Solomon Islands , Bioactive compounds , Extraction (Chemistry)
Call No.: pac QP 632 .M37 P7372 2011
Copyright:Under 10% of this thesis may be copied without the authors written permission
Abstract: This thesis describes the isolation and structural elucidation of bioactive compounds from a marine sponge of genus Melophlus collected from the Solomon Islands. The sponge under investigation belongs to the family Ancorinidae under the order Astrophorida. Screening of the crude extract for anti-microbial activity against methicillin resistant Staphylococcus aureas, wild type Staphylococcus aureas, vancomycin resistant Enterococcus faecium, wild type Candida albicans and amphotericin resistant Candida albicans was carried out. In addition, cytotoxicity was checked using the brine shrimp assay. Preliminary bioassay results showed that the crude extract exhibited anti-candida activity as well as cytotoxic properties. Bioassay guided fractionation utilising isolation techniques such as solvent-solvent partitioning, vacuum liquid chromatography, flash column chromatography together with purification by semi-preparative HPLC resulted in the discovery of four cytotoxic compounds. Two known cyclic depsipeptides termed papuamides C (compound III) and D (compound I) together with the new analogues designated as papuamide E (compound IV) and F (compound II) have been isolated from the marine sponge Melophlus sp. The structures were determined by interpretation of the spectroscopic data (1H-NMR, HSQC, 1H-1H COSY, HMBC and HSQC-TOCSY) and LC-MS analysis, as well as with reference to the literature available on papuamides A-D. Papuamides C-F contains 11 amino acid residues which includes glycine (two residues), alanine, threonine (two residues), 3-4-dimethylglutamine, - methoxytyrosine, 3-methoxyalanine, 2-amino-2-butenoic acid, 3-hydroxyleucine and homoproline residues. In addition, papuamides C-D contain 2,3-dihydroxy-2,6,8- trimethyldeca-4,6-dienoic acid moiety which has been substituted in papuamide E and F with a 3-hydroxy-2,6,8-trimethyldeca-4,6-dienoic acid moiety. Moreover, papuamides C-F have been found to be cytotoxic with lethal dosage (LD50) values of 92ppm, 92ppm, 104ppm and 106ppm respectively. This is the first report documenting the LD50 of the known compounds papuamides C-D and the isolation of new analogues, papuamide E and F. This is also the first report stating the isolation of depsipeptides, papuamides C-F, from a marine sponge of the genus Melophlus.