Investigation of pharmaceutical residues and polybrominated diphenyl ethers in selected river estuaries and canal in Eastern Cape Province, South Africa
- Ohoro, Chinemerem Ruth https://orcid.org/ 0000-0002-8167-6314
- Authors: Ohoro, Chinemerem Ruth https://orcid.org/ 0000-0002-8167-6314
- Date: 2021-09
- Subjects: Marine pharmacology
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10353/21545 , vital:48878
- Description: The increasing global pollution by contaminants of emerging concern due to industrialization, development, and improper handling of industrial and domestic waste is alarming. Some of these emerging contaminants are endocrine disruptors and persistent organic pollutants. Two groups of compounds (pharmaceuticals and polybrominated diphenyl ethers (PBDEs)) were considered for this study. Pharmaceuticals are drugs which we take to cure and nourish human and animal bodies, ranging from antibiotics, stimulants, psychiatric, to hormonal recipes among others. They are potentially toxic and comprise chemicals or active ingredients capable of disrupting hormones. They have been related to human and aquatic organisms' ecological risks, such as feminization and masculinization of fish, cancer, and disruption of the immune system. In recent times, pharmaceuticals are being tested in the Rivers of South Africa. PBDEs are human influential chemicals usually incorporated into products such as flame retardants, which can travel over a long distance. They are hydrophobic, lipophilic, environmentally persistent, and easily absorbed by aquatic organisms. About 209 congeners exist, and BDE- 17, 47, 66, 100, 153, 154, and 183 are frequently detected in the environment. The higher brominated congeners can debrominate to more toxic and lower congeners. Though they have low acute toxicity, their effect of interfering with the thyroid gland is long-term. They pose a risk such as immunological, neurological, carcinogenicity, and reproductive disruption. Water and sediment samples considered for investigation were collected from five different sites (Buffalo River Estuary, Sundays River Estuary, Swartkops River Estuary, Nahoon River Estuary, and Markman Canal stormwater). These sites are located in the two major cities hosting the two major Ports (East London and Port Elizabeth) in the Eastern Cape Province of South Africa. Five sampling points were chosen for the collection of both water and sediment samples across three seasons that span from August to December in each of the mentioned sites. Nahoon River Estuary that was not sampled in winter seasons due to logistics and the global pandemic of year 2020; sediment sample was not collected at point NH5 for the spring season because of inaccessibility and topography of the sampling point. Ultrasonic extraction was utilized for sediment samples while SPE method with C-18 cartridges, was used to extract pharmaceuticals in water samples and for the purification of sediment extracts. A chromatographic column was employed for sediment purification. Analytes considered in this study were carbamazepine, caffeine, trimethoprim, sulfamethoxazole, and testosterone. Nahoon River Estuary and Markman canal were considered for investigation of water and sediments for PBDEs. The samples were processed for analysis immediately on arrival to the laboratory after being stored in an ice chest at 4 oC. Physicochemical properties of water samples were taken on site. The temperature ranges from 15.5-24.5 oC for Markman and 24.5- 26.6 oC. Nahoon River Estuary. There was a correlation among the congeners except for BDE-153, which do not correlate with BDE- 17, 47, and 183 in Markman. However, BDE- 153 correlated with BDE-66 in Markman. The Ʃ5PBDE for water and Ʃ6PBDE sediment for all seasons were BDL – 1357 ng/L and BDL – 408.14 ng/g, respectively. The PBDEs mean concentrations in Nahoon water samples ranges from BDL-247 ng/L (spring). The dominant congeners in Nahoon Estuary and Markman Canal samples were BDE- 17 and BDE – 66. The temperature and pH of Swartkops River Estuary range from 16.66 – 25.15 oC, and 8.1 – 10.4, respectively. The pH of the Estuary was higher than that of the Markman Canal. The concentrations of pharmaceuticals in water samples were below detection limit. However, carbamazepine gave the highest concentration in sediment samples (23.86 μg/kg). SLF was not detected in sediment samples. The range of temperature for Buffalo River Estuary was lower than the other sites (18.10 – 20.22 oC); however, the pH showed no difference. Human and ecotoxicological risks were estimated for Markman Canal, Nahoon, Swartkops, Buffalo and Sundays River estuaries. The concentrations obtained for the two classes of contaminants in this study showed that PBDEs in Markman Canal sediment could pose a potential risk to humans, while Nahoon River Estuary poses no risk from PBDEs. Furthermore, the concentrations of caffeine in surface water of Sundays Estuary indicates low ecotoxicological risk to aquatic organisms (fish). Also, carbamazepine and trimethoprim levels (BDL – 9.50 and 1.39-2.00 μg/kg, respectively) suggest a high risk to aquatic organisms (bacteria, invertebrate, algae) in sediment of Buffalo, Sundays, and Swartkops estuaries, as well as Markman Canal. The situation report shows that the estuaries and canal in East London and Port Elizabeth are polluted by organic pollutants such as pharmaceuticals and polybrominated diphenyl ethers. Measures has to be taken to monitor the pollution of these rivers that are of economic value to South Africa. , Thesis (PhD) -- Faculty of Science and Agriculture, 2021
- Full Text:
- Date Issued: 2021-09
- Authors: Ohoro, Chinemerem Ruth https://orcid.org/ 0000-0002-8167-6314
- Date: 2021-09
- Subjects: Marine pharmacology
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10353/21545 , vital:48878
- Description: The increasing global pollution by contaminants of emerging concern due to industrialization, development, and improper handling of industrial and domestic waste is alarming. Some of these emerging contaminants are endocrine disruptors and persistent organic pollutants. Two groups of compounds (pharmaceuticals and polybrominated diphenyl ethers (PBDEs)) were considered for this study. Pharmaceuticals are drugs which we take to cure and nourish human and animal bodies, ranging from antibiotics, stimulants, psychiatric, to hormonal recipes among others. They are potentially toxic and comprise chemicals or active ingredients capable of disrupting hormones. They have been related to human and aquatic organisms' ecological risks, such as feminization and masculinization of fish, cancer, and disruption of the immune system. In recent times, pharmaceuticals are being tested in the Rivers of South Africa. PBDEs are human influential chemicals usually incorporated into products such as flame retardants, which can travel over a long distance. They are hydrophobic, lipophilic, environmentally persistent, and easily absorbed by aquatic organisms. About 209 congeners exist, and BDE- 17, 47, 66, 100, 153, 154, and 183 are frequently detected in the environment. The higher brominated congeners can debrominate to more toxic and lower congeners. Though they have low acute toxicity, their effect of interfering with the thyroid gland is long-term. They pose a risk such as immunological, neurological, carcinogenicity, and reproductive disruption. Water and sediment samples considered for investigation were collected from five different sites (Buffalo River Estuary, Sundays River Estuary, Swartkops River Estuary, Nahoon River Estuary, and Markman Canal stormwater). These sites are located in the two major cities hosting the two major Ports (East London and Port Elizabeth) in the Eastern Cape Province of South Africa. Five sampling points were chosen for the collection of both water and sediment samples across three seasons that span from August to December in each of the mentioned sites. Nahoon River Estuary that was not sampled in winter seasons due to logistics and the global pandemic of year 2020; sediment sample was not collected at point NH5 for the spring season because of inaccessibility and topography of the sampling point. Ultrasonic extraction was utilized for sediment samples while SPE method with C-18 cartridges, was used to extract pharmaceuticals in water samples and for the purification of sediment extracts. A chromatographic column was employed for sediment purification. Analytes considered in this study were carbamazepine, caffeine, trimethoprim, sulfamethoxazole, and testosterone. Nahoon River Estuary and Markman canal were considered for investigation of water and sediments for PBDEs. The samples were processed for analysis immediately on arrival to the laboratory after being stored in an ice chest at 4 oC. Physicochemical properties of water samples were taken on site. The temperature ranges from 15.5-24.5 oC for Markman and 24.5- 26.6 oC. Nahoon River Estuary. There was a correlation among the congeners except for BDE-153, which do not correlate with BDE- 17, 47, and 183 in Markman. However, BDE- 153 correlated with BDE-66 in Markman. The Ʃ5PBDE for water and Ʃ6PBDE sediment for all seasons were BDL – 1357 ng/L and BDL – 408.14 ng/g, respectively. The PBDEs mean concentrations in Nahoon water samples ranges from BDL-247 ng/L (spring). The dominant congeners in Nahoon Estuary and Markman Canal samples were BDE- 17 and BDE – 66. The temperature and pH of Swartkops River Estuary range from 16.66 – 25.15 oC, and 8.1 – 10.4, respectively. The pH of the Estuary was higher than that of the Markman Canal. The concentrations of pharmaceuticals in water samples were below detection limit. However, carbamazepine gave the highest concentration in sediment samples (23.86 μg/kg). SLF was not detected in sediment samples. The range of temperature for Buffalo River Estuary was lower than the other sites (18.10 – 20.22 oC); however, the pH showed no difference. Human and ecotoxicological risks were estimated for Markman Canal, Nahoon, Swartkops, Buffalo and Sundays River estuaries. The concentrations obtained for the two classes of contaminants in this study showed that PBDEs in Markman Canal sediment could pose a potential risk to humans, while Nahoon River Estuary poses no risk from PBDEs. Furthermore, the concentrations of caffeine in surface water of Sundays Estuary indicates low ecotoxicological risk to aquatic organisms (fish). Also, carbamazepine and trimethoprim levels (BDL – 9.50 and 1.39-2.00 μg/kg, respectively) suggest a high risk to aquatic organisms (bacteria, invertebrate, algae) in sediment of Buffalo, Sundays, and Swartkops estuaries, as well as Markman Canal. The situation report shows that the estuaries and canal in East London and Port Elizabeth are polluted by organic pollutants such as pharmaceuticals and polybrominated diphenyl ethers. Measures has to be taken to monitor the pollution of these rivers that are of economic value to South Africa. , Thesis (PhD) -- Faculty of Science and Agriculture, 2021
- Full Text:
- Date Issued: 2021-09
Marine anti-malarial isonitriles : a synthetic and computational study
- Authors: Adendorff, Matthew Ralph
- Date: 2011 , 2010-05-17
- Subjects: Isocyanides , Isocyanates , Marine pharmacology , Antimalarials , Antimalarials -- Development , Drug development
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4398 , http://hdl.handle.net/10962/d1006674 , Isocyanides , Isocyanates , Marine pharmacology , Antimalarials , Antimalarials -- Development , Drug development
- Description: The development of Plasmodium falciparum malarial resistance to the current armoury of anti-malarial drugs requires the development of new treatments to help combat this disease. The marine environment is a well established source of potential pharmaceuticals. Of interest to us are isonitrile, isocyanate and isothiocyanate compounds isolated from marine sponges and molluscs which have exhibited nano-molar anti-plasmodial activities. Through quantitative structure-activity relation studies (QSAR), a literature precedent exists for a pseudoreceptor model from which a pharmacophore for the design of novel anti-malarial agents was proposed. The current theory suggests that these marine compounds exert their inhibitory action through interfering with the heme detoxification pathway in P. falciparum. We propose that the computational methods used to draw detailed conclusions about the mode of action of these marine compounds were inadequate. This thesis addresses this problem using contemporary computational methodologies and seeks to propose a more robust method for the rational design of new anti-malarial drug compounds that inhibit heme polymerization to hemozoin. In order to investigate the interactions of the marine compounds with their heme targets, a series of modern computational procedures were formulated, validated and then applied to theoretical systems. The validations of these algorithms, before their application to the marine compound-heme systems, were achieved through two case studies. The first was used to investigate the applicability of the statistical docking algorithm AutoDock to be used for the exploration of conformational space around the heme target. A theoretical P. falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR) enzyme model, constructed by the Biochemistry Department at Rhodes University, provided the ideal model to validate the AutoDock program. The protein model was accordingly subjected to rigorous docking simulations with over 30 different ligand molecules using the AutoDock algorithm which allowed for the docking algorithm’s limitations to be ascertained and improved upon. This investigation facilitated the successful validation of the protein model, which can now be used for the rational design of new PfDXR-inhibiting anti-plasmodial compounds, as well as enabling us to propose an improvement of the docking algorithm for application to the heme systems. The second case study was used to investigate the applicability of an ab initio molecular dynamics algorithm for simulation of bond breaking/forming events between the marine compounds and their heme target. This validation involved the exploration of intermolecular interactions in a naturally occurring nonoligomeric zipper using the Car-Parrinello Molecular Dynamics (CPMD) method. This study allowed us to propose a model for the intermolecular forces responsible for zipper self-assembly and showcased the CPMD method’s abilities to simulate and predict bond forming/breaking events. Data from the computational analyses suggested that the interactions between marine isonitriles, isocyanates and isothiocyanates occur through bond-less electrostatic attractions rather than through formal intermolecular bonds as had been previously suggested. Accordingly, a simple bicyclic tertiary isonitrile (5.14) was synthesized using Kitano et al’s relatively underutilized isonitrile synthetic method for the conversion of tertiary alcohols to their corresponding isonitriles. This compound’s potential for heme detoxification inhibition was then explored in vitro via the pyridine-hemochrome assay. The assay data suggested that the synthesized isonitrile was capable of inhibiting heme polymerization in a similar fashion to the known inhibitor chloroquine. Attempts to synthesize tricyclic analogues of 5.14 were unsuccessful and highlighted the limitation of Kitano et al’s isonitrile synthetic methodology.
- Full Text:
- Date Issued: 2011
- Authors: Adendorff, Matthew Ralph
- Date: 2011 , 2010-05-17
- Subjects: Isocyanides , Isocyanates , Marine pharmacology , Antimalarials , Antimalarials -- Development , Drug development
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4398 , http://hdl.handle.net/10962/d1006674 , Isocyanides , Isocyanates , Marine pharmacology , Antimalarials , Antimalarials -- Development , Drug development
- Description: The development of Plasmodium falciparum malarial resistance to the current armoury of anti-malarial drugs requires the development of new treatments to help combat this disease. The marine environment is a well established source of potential pharmaceuticals. Of interest to us are isonitrile, isocyanate and isothiocyanate compounds isolated from marine sponges and molluscs which have exhibited nano-molar anti-plasmodial activities. Through quantitative structure-activity relation studies (QSAR), a literature precedent exists for a pseudoreceptor model from which a pharmacophore for the design of novel anti-malarial agents was proposed. The current theory suggests that these marine compounds exert their inhibitory action through interfering with the heme detoxification pathway in P. falciparum. We propose that the computational methods used to draw detailed conclusions about the mode of action of these marine compounds were inadequate. This thesis addresses this problem using contemporary computational methodologies and seeks to propose a more robust method for the rational design of new anti-malarial drug compounds that inhibit heme polymerization to hemozoin. In order to investigate the interactions of the marine compounds with their heme targets, a series of modern computational procedures were formulated, validated and then applied to theoretical systems. The validations of these algorithms, before their application to the marine compound-heme systems, were achieved through two case studies. The first was used to investigate the applicability of the statistical docking algorithm AutoDock to be used for the exploration of conformational space around the heme target. A theoretical P. falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR) enzyme model, constructed by the Biochemistry Department at Rhodes University, provided the ideal model to validate the AutoDock program. The protein model was accordingly subjected to rigorous docking simulations with over 30 different ligand molecules using the AutoDock algorithm which allowed for the docking algorithm’s limitations to be ascertained and improved upon. This investigation facilitated the successful validation of the protein model, which can now be used for the rational design of new PfDXR-inhibiting anti-plasmodial compounds, as well as enabling us to propose an improvement of the docking algorithm for application to the heme systems. The second case study was used to investigate the applicability of an ab initio molecular dynamics algorithm for simulation of bond breaking/forming events between the marine compounds and their heme target. This validation involved the exploration of intermolecular interactions in a naturally occurring nonoligomeric zipper using the Car-Parrinello Molecular Dynamics (CPMD) method. This study allowed us to propose a model for the intermolecular forces responsible for zipper self-assembly and showcased the CPMD method’s abilities to simulate and predict bond forming/breaking events. Data from the computational analyses suggested that the interactions between marine isonitriles, isocyanates and isothiocyanates occur through bond-less electrostatic attractions rather than through formal intermolecular bonds as had been previously suggested. Accordingly, a simple bicyclic tertiary isonitrile (5.14) was synthesized using Kitano et al’s relatively underutilized isonitrile synthetic method for the conversion of tertiary alcohols to their corresponding isonitriles. This compound’s potential for heme detoxification inhibition was then explored in vitro via the pyridine-hemochrome assay. The assay data suggested that the synthesized isonitrile was capable of inhibiting heme polymerization in a similar fashion to the known inhibitor chloroquine. Attempts to synthesize tricyclic analogues of 5.14 were unsuccessful and highlighted the limitation of Kitano et al’s isonitrile synthetic methodology.
- Full Text:
- Date Issued: 2011
A study of plocamium corallorhiza secondary metabolites and their biological activity
- Authors: Mkwananzi, Henry Bayanda
- Date: 2005
- Subjects: Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3841 , http://hdl.handle.net/10962/d1007666 , Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Description: Seaweeds of the genus Plocamium are known to produce a variety of halogenated monoterpenes. In addition to their ecological role as feeding deterrents, biological activities reported for these compounds include antibacterial, antialgal, antifungal and anticancer activities. An investigation of the non-polar extracts of the seaweed Plocamium corallorhiza resulted in the isolation of six known halogenated monoterpene compounds, 4-bromo-5-bromomethyl-1-chlorovinyl-2, 5-dichloro-methylcyclohexane (2.68), 1,4,8-tribromo-3 ,7-dichloro-3, 7-dimethyl-1,5-octadiene (2.67), 8-bromo-1 ,3,4,7-tetrachloro-3, 7-dimethyl-1,5-octadiene (2.66), 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2,7-octadiene (2.64), 4,8-dibromo-1,1,7-trichloro-3,7-dimethyl-2,5-octadiene (2.65) and 3,4 ,6,7-tetrachloro-3, 7-dimethyl-1-octene (2.63) as well as eight new compounds, including five halogenated monoterpene aldehydes. The new compounds were identified by 1D and 2D NMR spectroscopic techniques as: 8-Bromo-6,7-dichloro-3,7-dimethyl-octa-2,4-dienal (2.72), 8-Bromo-1,1,2,7-tetrachloro-3,7-dimethyl-octa-3,5-diene (2.70), 4,8-Dichloro-3,7-dimethyl-octa-2,4,6-trienal (2.74), 4-Bromo-8-chloro-3, 7-di methyl-octa-2, 6-dienal (2 76), 8-Bromo-4-chloro-3, 7-dimethyl-octa-2,4 ,6-trienaI (2.75), 4-Bromo-1,3,6,7-tetrachloro-3 ,7-dimethyl-octa-1,4-diene (2.71), 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-octa-1,5-diene (2.69), 4,6-Dibromo-3,7 -dimethyl-octa-2,7-dienal (2.73). All compounds were screened for antimicrobial activity, brine shrimp lethality and cytotoxicity towards oesophageal cancer cells. Compound 2.68 was toxic to brine shrimp larvae at a concentration of 50 μ/mL. It also showed promising activity towards oesophageal cancer cells with an IC₅₀, of 2 μg/mL.
- Full Text:
- Date Issued: 2005
- Authors: Mkwananzi, Henry Bayanda
- Date: 2005
- Subjects: Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3841 , http://hdl.handle.net/10962/d1007666 , Natural products -- Therapeutic use , Marine metabolites -- Therapeutic use , Marine pharmacology , Marine algae , Monoterpenes
- Description: Seaweeds of the genus Plocamium are known to produce a variety of halogenated monoterpenes. In addition to their ecological role as feeding deterrents, biological activities reported for these compounds include antibacterial, antialgal, antifungal and anticancer activities. An investigation of the non-polar extracts of the seaweed Plocamium corallorhiza resulted in the isolation of six known halogenated monoterpene compounds, 4-bromo-5-bromomethyl-1-chlorovinyl-2, 5-dichloro-methylcyclohexane (2.68), 1,4,8-tribromo-3 ,7-dichloro-3, 7-dimethyl-1,5-octadiene (2.67), 8-bromo-1 ,3,4,7-tetrachloro-3, 7-dimethyl-1,5-octadiene (2.66), 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2,7-octadiene (2.64), 4,8-dibromo-1,1,7-trichloro-3,7-dimethyl-2,5-octadiene (2.65) and 3,4 ,6,7-tetrachloro-3, 7-dimethyl-1-octene (2.63) as well as eight new compounds, including five halogenated monoterpene aldehydes. The new compounds were identified by 1D and 2D NMR spectroscopic techniques as: 8-Bromo-6,7-dichloro-3,7-dimethyl-octa-2,4-dienal (2.72), 8-Bromo-1,1,2,7-tetrachloro-3,7-dimethyl-octa-3,5-diene (2.70), 4,8-Dichloro-3,7-dimethyl-octa-2,4,6-trienal (2.74), 4-Bromo-8-chloro-3, 7-di methyl-octa-2, 6-dienal (2 76), 8-Bromo-4-chloro-3, 7-dimethyl-octa-2,4 ,6-trienaI (2.75), 4-Bromo-1,3,6,7-tetrachloro-3 ,7-dimethyl-octa-1,4-diene (2.71), 8-Bromo-1,3,4,7-tetrachloro-3,7-dimethyl-octa-1,5-diene (2.69), 4,6-Dibromo-3,7 -dimethyl-octa-2,7-dienal (2.73). All compounds were screened for antimicrobial activity, brine shrimp lethality and cytotoxicity towards oesophageal cancer cells. Compound 2.68 was toxic to brine shrimp larvae at a concentration of 50 μ/mL. It also showed promising activity towards oesophageal cancer cells with an IC₅₀, of 2 μg/mL.
- Full Text:
- Date Issued: 2005
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