Bioactive 4-methoxypyrrolic natural products from two South African marine invertebrates
- Authors: Rapson, Trevor Douglas
- Date: 2005
- Subjects: Natural products -- South Africa , Marine invertebrates -- South Africa , Bryozoa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4412 , http://hdl.handle.net/10962/d1006766 , Natural products -- South Africa , Marine invertebrates -- South Africa , Bryozoa
- Description: This thesis presents an investigation of the 4-methoxypyrrolic constituents of two South African marine invertebrates, the nudibranch Tambja capensis and the bryozoan Bugula dentata. Three known compounds tambjamine A (7), tambjamine E (13) and the tetrapyrrole (15) were isolated during this investigation. All three compounds were shown to be active against oesophageal cancer in accordance with the general anticancer and immunosuppressive properties observed for 4-methoxypyrrolic natural products. Tambjamine A (7), tambjamine E (13) and the tetrapyrrole (15), together with tambjamine K (21) and L (22) (previously isolated in our laboratory) were used as standards to quantitatively assess the presence of these tambjamines in T. capensis and B. dentata collected from three different sites along the South African coast. This study confirmed that B. dentata is the source of the 4-methoxypyrrolic natural products sequestered by T. capensis and eliminated the closely related bryozoan B. neritina as a source of these metabolites. The paucity of tambjamine L (21) and K (22) obtained in previous investigations of the sequestered chemistry of T. capensis prompted an attempt at the development of synthetic methodology that could be used to synthesize tambjamines in sufficient yield for in depth bioactivity studies. In order to by pass the extensively reported problems associated with the synthesis of this group of compound 3-methoxy-2-formylpyrrole (47), readily accessible from 3-methoxypyridine N-oxide (48), was used as the starting material in a singlet oxygen induced 2,2’ bipyrrole coupling reaction. Although 47 proved unreactive in this coupling reaction, when the N-Boc protected analogue of 47 was used, and the reaction worked up in the dark, the novel methyl 4-aza-5-oxo-6,6-di-(2-pyrrolyl)-2(Z)-hexenoate (57) was obtained in low yield. The physical properties of tambjamine (E) (13) and the tetrapyrrole (15) were investigated to further the understanding of the proposed oxidative DNA cleavage mechanism and to determine the potential of the 4-methoxypyrrolic natural products as photodynamic therapy agents.
- Full Text:
- Date Issued: 2005
- Authors: Rapson, Trevor Douglas
- Date: 2005
- Subjects: Natural products -- South Africa , Marine invertebrates -- South Africa , Bryozoa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4412 , http://hdl.handle.net/10962/d1006766 , Natural products -- South Africa , Marine invertebrates -- South Africa , Bryozoa
- Description: This thesis presents an investigation of the 4-methoxypyrrolic constituents of two South African marine invertebrates, the nudibranch Tambja capensis and the bryozoan Bugula dentata. Three known compounds tambjamine A (7), tambjamine E (13) and the tetrapyrrole (15) were isolated during this investigation. All three compounds were shown to be active against oesophageal cancer in accordance with the general anticancer and immunosuppressive properties observed for 4-methoxypyrrolic natural products. Tambjamine A (7), tambjamine E (13) and the tetrapyrrole (15), together with tambjamine K (21) and L (22) (previously isolated in our laboratory) were used as standards to quantitatively assess the presence of these tambjamines in T. capensis and B. dentata collected from three different sites along the South African coast. This study confirmed that B. dentata is the source of the 4-methoxypyrrolic natural products sequestered by T. capensis and eliminated the closely related bryozoan B. neritina as a source of these metabolites. The paucity of tambjamine L (21) and K (22) obtained in previous investigations of the sequestered chemistry of T. capensis prompted an attempt at the development of synthetic methodology that could be used to synthesize tambjamines in sufficient yield for in depth bioactivity studies. In order to by pass the extensively reported problems associated with the synthesis of this group of compound 3-methoxy-2-formylpyrrole (47), readily accessible from 3-methoxypyridine N-oxide (48), was used as the starting material in a singlet oxygen induced 2,2’ bipyrrole coupling reaction. Although 47 proved unreactive in this coupling reaction, when the N-Boc protected analogue of 47 was used, and the reaction worked up in the dark, the novel methyl 4-aza-5-oxo-6,6-di-(2-pyrrolyl)-2(Z)-hexenoate (57) was obtained in low yield. The physical properties of tambjamine (E) (13) and the tetrapyrrole (15) were investigated to further the understanding of the proposed oxidative DNA cleavage mechanism and to determine the potential of the 4-methoxypyrrolic natural products as photodynamic therapy agents.
- Full Text:
- Date Issued: 2005
Marine biotechnology : evaluation and development of methods for the discovery of natural products from fungi
- Authors: Pather, Simisha
- Date: 2005 , 2013-06-18
- Subjects: Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3839 , http://hdl.handle.net/10962/d1007652 , Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Description: One of the major impediments in the development of marine natural products is the provision of biologically active natural products in sufficient quantity for complete pharmacological evaluation, clinical trials and eventual commercial production. Marine microorganisms show great promise in providing a renewable source of biologically active natural products. The main aim of this study was to develop and evaluate methods for the isolation, identification and cultivation of marine fungi from the South African marine environment for the production of biologically active secondary metabolites. Twenty-four species of fungi were isolated from marine algae collected from the intertidal zone near Port Alfred, South Africa. The fungi were cultivated in small-scale under static and agitated conditions and their crude intra- and extracellular organic extracts were screened by ¹H NMR and a series of bioassays. Using this as a basis, one isolate was selected for further study. By analyses of the lTS1 region of the ribosomal DNA, the fungal isolate was identified as a marine-derived isolate of Eurotium rubrum (Aspergillus ruber). Although E. rubrum has been isolated from the marine environment, no investigations have been undertaken to determine the adaptation of these isolates to the marine environment. In order to optimise productivity, creativity and incubation time, the fungus was cultivated in small-scale using a variety of carbon (glucose, fructose, lactose, sucrose, marmitol and maltose) and nitrogen sources (ammonium tartrate, urea, peptone and yeast extract). An HPLC-DAD method was developed to assess the metabolic creativity and productivity under different fermentation conditions. Distinctive variations in the range and yield of metabolites produced as well as morphology and growth time were observed. The crude extracts from all fermentations were combined and six known compounds were isolated by reversed-phase chromatography and their structures elucidated by spectroscopic techniques. The known compounds were fIavoglaucin, aspergin, isodihydroauroglaucin, isotetrahydroauroglaucin, neoechinuline A and physcion. Neoechinuline A, isodihydroauroglaucin and isotetrahydroauroglaucin showed activity against oesophageal and cervical cancer cell lines.
- Full Text:
- Date Issued: 2005
- Authors: Pather, Simisha
- Date: 2005 , 2013-06-18
- Subjects: Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3839 , http://hdl.handle.net/10962/d1007652 , Marine biotechnology , Marine fungi -- South Africa , Natural products -- South Africa , Marine plants -- South Africa , Marine metabolites -- South Africa , Cancer -- Treatment , DNA
- Description: One of the major impediments in the development of marine natural products is the provision of biologically active natural products in sufficient quantity for complete pharmacological evaluation, clinical trials and eventual commercial production. Marine microorganisms show great promise in providing a renewable source of biologically active natural products. The main aim of this study was to develop and evaluate methods for the isolation, identification and cultivation of marine fungi from the South African marine environment for the production of biologically active secondary metabolites. Twenty-four species of fungi were isolated from marine algae collected from the intertidal zone near Port Alfred, South Africa. The fungi were cultivated in small-scale under static and agitated conditions and their crude intra- and extracellular organic extracts were screened by ¹H NMR and a series of bioassays. Using this as a basis, one isolate was selected for further study. By analyses of the lTS1 region of the ribosomal DNA, the fungal isolate was identified as a marine-derived isolate of Eurotium rubrum (Aspergillus ruber). Although E. rubrum has been isolated from the marine environment, no investigations have been undertaken to determine the adaptation of these isolates to the marine environment. In order to optimise productivity, creativity and incubation time, the fungus was cultivated in small-scale using a variety of carbon (glucose, fructose, lactose, sucrose, marmitol and maltose) and nitrogen sources (ammonium tartrate, urea, peptone and yeast extract). An HPLC-DAD method was developed to assess the metabolic creativity and productivity under different fermentation conditions. Distinctive variations in the range and yield of metabolites produced as well as morphology and growth time were observed. The crude extracts from all fermentations were combined and six known compounds were isolated by reversed-phase chromatography and their structures elucidated by spectroscopic techniques. The known compounds were fIavoglaucin, aspergin, isodihydroauroglaucin, isotetrahydroauroglaucin, neoechinuline A and physcion. Neoechinuline A, isodihydroauroglaucin and isotetrahydroauroglaucin showed activity against oesophageal and cervical cancer cell lines.
- Full Text:
- Date Issued: 2005
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