The impact of Information and Communication Technology (ICT) on effective teaching of environmental education in rural high schools
- Authors: Mireku, Akosua Agyakoma
- Date: 2016
- Subjects: Educational technology -- South -- Africa Communication -- Technological innovations Rural development -- South Africa
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10353/5675 , vital:29360
- Description: Information and Communication Technology (ICT) has become commonplace entities in all aspects of life. Over the past twenty years, the use of ICTs has drastically changed the procedures of almost all forms of endeavour within business and governance. Additionally, throughout the world there is an awareness of the fundamental role of new ICTs in the field of education. Education is a socially oriented activity, and quality education has traditionally been associated with strong teachers having high degrees of personal contact with learners. The use of ICT in education lends itself to learner-centred learning settings. With the world moving rapidly into digital media and information, the role of ICT in education and the influence of ICT in schools cannot be overemphasised as its utility is changing the way learners learn, teachers teach, and how it supports staff work. Whilst ICT is fully integrated into many schools in the urban areas of South Africa, regrettably the same cannot be said about rural high schools. This has created a digital division between rural and urban high schools. Most of these rural high schools still do not have access to these technological tools and educators have not been given the professional training for them to integrate ICT in their lessons. This study explores the effectiveness of integrating ICT into teaching of Environmental Education in selected rural high schools. The quantitative study adopted survey research design with sample randomly selected for the study. From the findings, it can be concluded that integrating ICT in education cannot be comprehended by exploring the pedagogical orientations at play in the teaching and learning situation. It becomes the basis that teachers use ICTs to achieve the determined goals.
- Full Text:
- Date Issued: 2016
- Authors: Mireku, Akosua Agyakoma
- Date: 2016
- Subjects: Educational technology -- South -- Africa Communication -- Technological innovations Rural development -- South Africa
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: http://hdl.handle.net/10353/5675 , vital:29360
- Description: Information and Communication Technology (ICT) has become commonplace entities in all aspects of life. Over the past twenty years, the use of ICTs has drastically changed the procedures of almost all forms of endeavour within business and governance. Additionally, throughout the world there is an awareness of the fundamental role of new ICTs in the field of education. Education is a socially oriented activity, and quality education has traditionally been associated with strong teachers having high degrees of personal contact with learners. The use of ICT in education lends itself to learner-centred learning settings. With the world moving rapidly into digital media and information, the role of ICT in education and the influence of ICT in schools cannot be overemphasised as its utility is changing the way learners learn, teachers teach, and how it supports staff work. Whilst ICT is fully integrated into many schools in the urban areas of South Africa, regrettably the same cannot be said about rural high schools. This has created a digital division between rural and urban high schools. Most of these rural high schools still do not have access to these technological tools and educators have not been given the professional training for them to integrate ICT in their lessons. This study explores the effectiveness of integrating ICT into teaching of Environmental Education in selected rural high schools. The quantitative study adopted survey research design with sample randomly selected for the study. From the findings, it can be concluded that integrating ICT in education cannot be comprehended by exploring the pedagogical orientations at play in the teaching and learning situation. It becomes the basis that teachers use ICTs to achieve the determined goals.
- Full Text:
- Date Issued: 2016
Representations of the ‘other’: a comparison between Roman descriptions of Britons, Gauls and Germans pre-AD 300 and Sir Harry Smith’s portrayal of the Xhosa 1830s – 1850s
- Authors: Van Wezel, Amy Hester
- Date: 2016
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/4223 , vital:20634
- Description: Stereotypical representations of an ‘ethnically’ or ‘racially’ different ‘other’ in ancient texts would seem to reappear throughout history. By comparing Roman views of Britons, Gauls and Germans, with Sir Harry Smith’s views of the Xhosa, this study seeks to explore the extent to which these stereotypical images were employed and for what reasons. Through close textual analyses, the descriptions of these peoples are examined and compared, taking into consideration the different authors’ context and agendas. By highlighting Caesar’s views of the abilities of the ‘other’ and Tacitus’ judgements of the moral character of the ‘other’, compared with Smith’s view of the same, the study aims to draw out the role of the author’s ‘self’ in complex and contradictory representations of the ‘other’, while arguing that various overwhelmingly negative images served to justify imperial conquest and rule. The extent to which the ‘other’ was perceived as remote and different from themselves, epitomised in the dichotomy between the ‘barbarism’ and ‘civilisation’, is examined, comparing a variety of Roman authors with Smith. The similar idea of ‘civilising missions’ are discussed, while acknowledging the differences between the policies of the Roman and British Empires toward the ‘other’. The connections between how the ‘other’ was portrayed in relation to ‘Empire’ and the ways in which they were treated is also explored stressing even further the different approaches taken by Roman and British authorities to include these peoples within their Empires. While certain stereotypes are shown to have persisted from Roman times, reappearing in the writing of Sir Harry Smith, summed up in the archetypal ‘barbarian’, I argue that the use of these images was varied, inconsistent and reflected more the motives and personalities of the writers themselves, whofor the most part ascribed to imperial ideologies.
- Full Text:
- Date Issued: 2016
- Authors: Van Wezel, Amy Hester
- Date: 2016
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/4223 , vital:20634
- Description: Stereotypical representations of an ‘ethnically’ or ‘racially’ different ‘other’ in ancient texts would seem to reappear throughout history. By comparing Roman views of Britons, Gauls and Germans, with Sir Harry Smith’s views of the Xhosa, this study seeks to explore the extent to which these stereotypical images were employed and for what reasons. Through close textual analyses, the descriptions of these peoples are examined and compared, taking into consideration the different authors’ context and agendas. By highlighting Caesar’s views of the abilities of the ‘other’ and Tacitus’ judgements of the moral character of the ‘other’, compared with Smith’s view of the same, the study aims to draw out the role of the author’s ‘self’ in complex and contradictory representations of the ‘other’, while arguing that various overwhelmingly negative images served to justify imperial conquest and rule. The extent to which the ‘other’ was perceived as remote and different from themselves, epitomised in the dichotomy between the ‘barbarism’ and ‘civilisation’, is examined, comparing a variety of Roman authors with Smith. The similar idea of ‘civilising missions’ are discussed, while acknowledging the differences between the policies of the Roman and British Empires toward the ‘other’. The connections between how the ‘other’ was portrayed in relation to ‘Empire’ and the ways in which they were treated is also explored stressing even further the different approaches taken by Roman and British authorities to include these peoples within their Empires. While certain stereotypes are shown to have persisted from Roman times, reappearing in the writing of Sir Harry Smith, summed up in the archetypal ‘barbarian’, I argue that the use of these images was varied, inconsistent and reflected more the motives and personalities of the writers themselves, whofor the most part ascribed to imperial ideologies.
- Full Text:
- Date Issued: 2016
An erosion and sediment delivery model for semi-arid catchments
- Authors: Bryson, Louise Kay
- Date: 2016
- Subjects: Sedimentation and deposition , Erosion , Watershed management -- South Africa , Water-supply -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:6056 , http://hdl.handle.net/10962/d1020331
- Description: Sedimentation has become a significant environmental threat in South Africa as it intensifies water management problems in the water-scarce semi-arid regions of the country. As South Africa already allocates 98% of available water, the loss of storage capacity in reservoirs and degraded water quality has meant that a reliable water supply is compromised. The overall aim of this thesis was to develop a catchment scale model that represents the sediment dynamics of semi-arid regions of South Africa as a simple and practically applicable tool for water resource managers. Development of a conceptual framework for the model relied on an understanding of both the sediment dynamics of South African catchments and applicable modelling techniques. Scale was an issue in both cases as most of our understanding of the physical processes of runoff generation and sediment transport has been derived from plot scale studies. By identifying defining properties of semi-arid catchments it was possible to consider how temporal and spatial properties at higher levels emerged from properties at lower levels. These properties were effectively represented by using the Pitman rainfall-runoff model disaggregated to a daily timescale, the Modified Universal Soil Loss Equation (MUSLE) model incorporating probability function theory and through the representation of sediment storages across a semi-distributed catchment. The model was tested on two small and one large study catchment in the Karoo, South Africa, with limited observed data. Limitations to the model were found to be the large parameter data set and the dominance of structural constraints with an increase in catchment size. The next steps in model development will require a reduction of the parameter data set and an inclusion of an in-stream component for sub-catchments at a larger spatial scale. The model is applicable in areas such as South Africa where water resource managers need a simple model at the catchment scale in order to make decisions. This type of model provides a simple representation of the stochastic nature of erosion and sediment delivery over large spatial and temporal scales.
- Full Text:
- Date Issued: 2016
- Authors: Bryson, Louise Kay
- Date: 2016
- Subjects: Sedimentation and deposition , Erosion , Watershed management -- South Africa , Water-supply -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:6056 , http://hdl.handle.net/10962/d1020331
- Description: Sedimentation has become a significant environmental threat in South Africa as it intensifies water management problems in the water-scarce semi-arid regions of the country. As South Africa already allocates 98% of available water, the loss of storage capacity in reservoirs and degraded water quality has meant that a reliable water supply is compromised. The overall aim of this thesis was to develop a catchment scale model that represents the sediment dynamics of semi-arid regions of South Africa as a simple and practically applicable tool for water resource managers. Development of a conceptual framework for the model relied on an understanding of both the sediment dynamics of South African catchments and applicable modelling techniques. Scale was an issue in both cases as most of our understanding of the physical processes of runoff generation and sediment transport has been derived from plot scale studies. By identifying defining properties of semi-arid catchments it was possible to consider how temporal and spatial properties at higher levels emerged from properties at lower levels. These properties were effectively represented by using the Pitman rainfall-runoff model disaggregated to a daily timescale, the Modified Universal Soil Loss Equation (MUSLE) model incorporating probability function theory and through the representation of sediment storages across a semi-distributed catchment. The model was tested on two small and one large study catchment in the Karoo, South Africa, with limited observed data. Limitations to the model were found to be the large parameter data set and the dominance of structural constraints with an increase in catchment size. The next steps in model development will require a reduction of the parameter data set and an inclusion of an in-stream component for sub-catchments at a larger spatial scale. The model is applicable in areas such as South Africa where water resource managers need a simple model at the catchment scale in order to make decisions. This type of model provides a simple representation of the stochastic nature of erosion and sediment delivery over large spatial and temporal scales.
- Full Text:
- Date Issued: 2016
Codeswitching online: a case study of a bilingual online maths programme for grade 7 learners in Diepsloot, Johannesburg
- Authors: von Witt, Nathalia
- Date: 2016
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/3983 , vital:20577
- Description: There is an education crisis in South Africa. Mathematics and literacy are at the forefront of the problem, as particularly evidenced by Annual National Assessment results (Department of Basic Education, 2014; Spaull, 2014). This research is motivated by the unequal access to quality learning which stems from learners learning through a poorly-understood second language with little to no cognitive academic language proficiency. The vast majority of South African learners learn through their second language, English, from Grade 4 onwards. English is the language of South Africa’s political economy and is a global lingua franca; however, the understanding of concepts and content learnt at school is vital if one is to have any hope of putting one’s English to good use. This research aimed to find a way to equip learners both with English proficiency and mathematical understanding simultaneously. This was done by implementing and evaluating an experimental bilingual course in an existing mathematics programme in the township of Diepsloot in Johannesburg, South Africa. This research used design-based research methodology, using both qualitative and quantitative research methods. This methodology was chosen as it allows theory and practice to intersect in a real-life setting, and for the successes and shortcomings of this intersection to be evaluated. This study encompasses both the evaluation and creation of the bilingual online mathematics course. The course is made bilingual through the creation of bilingual videos with the use of translanguaging and the creation of a bilingual glossary of terms. The videos were created using a translanguaging ‘model’ informed by theories of basic interpersonal communication skills and cognitive academic language proficiency (Cummins, 1981), common underlying proficiency (Cummins, 1991), codeswitching (Setati, 1998; Ncoko et al., 2000) and translanguaging (Makalela 2015; Creese and Blackledge, 2010a). The aim of this research was to create a successful translanguaging model which facilitates learners’ ability to conceptualise in their first language and then discuss and understand the concept in their second language.
- Full Text:
- Date Issued: 2016
- Authors: von Witt, Nathalia
- Date: 2016
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/3983 , vital:20577
- Description: There is an education crisis in South Africa. Mathematics and literacy are at the forefront of the problem, as particularly evidenced by Annual National Assessment results (Department of Basic Education, 2014; Spaull, 2014). This research is motivated by the unequal access to quality learning which stems from learners learning through a poorly-understood second language with little to no cognitive academic language proficiency. The vast majority of South African learners learn through their second language, English, from Grade 4 onwards. English is the language of South Africa’s political economy and is a global lingua franca; however, the understanding of concepts and content learnt at school is vital if one is to have any hope of putting one’s English to good use. This research aimed to find a way to equip learners both with English proficiency and mathematical understanding simultaneously. This was done by implementing and evaluating an experimental bilingual course in an existing mathematics programme in the township of Diepsloot in Johannesburg, South Africa. This research used design-based research methodology, using both qualitative and quantitative research methods. This methodology was chosen as it allows theory and practice to intersect in a real-life setting, and for the successes and shortcomings of this intersection to be evaluated. This study encompasses both the evaluation and creation of the bilingual online mathematics course. The course is made bilingual through the creation of bilingual videos with the use of translanguaging and the creation of a bilingual glossary of terms. The videos were created using a translanguaging ‘model’ informed by theories of basic interpersonal communication skills and cognitive academic language proficiency (Cummins, 1981), common underlying proficiency (Cummins, 1991), codeswitching (Setati, 1998; Ncoko et al., 2000) and translanguaging (Makalela 2015; Creese and Blackledge, 2010a). The aim of this research was to create a successful translanguaging model which facilitates learners’ ability to conceptualise in their first language and then discuss and understand the concept in their second language.
- Full Text:
- Date Issued: 2016
Presentation and representation of environmental problems and problem-solving methods and processes in the Grade 10 Geography syllabus: a Namibian case study
- Authors: Zokka, Herman Kankara
- Date: 2016
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: vital:2074 , http://hdl.handle.net/10962/d1021253
- Description: Environmental issues in Namibia are considered to be one of the major threats to the lives of the Namibian people (Namibia. Ministry of National Planning Commission [MNPC], 2004). This study explored problem solving as one of the teaching methods used in Grade 10 Geography syllabuses as a response to such environmental issues/risks. Geography provides learners with an understanding of the issues and risks in their world that need to be addressed in order to improve the quality of their lives and health of their environment. This study focused on how environmental problems and problem-solving methods are presented in the Namibian Grade 10 Geography syllabus and how these are represented and implemented through teacher intentionality and practice. The theoretical framework for this study was informed by two theories namely risk society and social constructivism. This study was conducted at three schools in the Rundu circuit in the Kavango region and one teacher was involved in the study at each school. This study was conducted within an interpretive research tradition and was qualitative in nature. The study used document analysis, focus group discussion and classroom observation as data generation methods. The findings of the study reveal that the complexity of environmental issues is highlighted in the syllabus and in teachers’ intentionality and practice. The findings also show that a limited variety of teaching methods were used in problem solving strategies. The study also found that problem solving was influenced by different constructivist learning principles. The study further found that limited numbers of problem-solving steps were used in the process of problem solving. The study concludes by calling for further research into problem solving strategies. This can be done to empower Geography teachers to use more complex problem solving strategies to deepen problem solving and to engage problems in more depth.
- Full Text:
- Date Issued: 2016
- Authors: Zokka, Herman Kankara
- Date: 2016
- Language: English
- Type: Thesis , Masters , MEd
- Identifier: vital:2074 , http://hdl.handle.net/10962/d1021253
- Description: Environmental issues in Namibia are considered to be one of the major threats to the lives of the Namibian people (Namibia. Ministry of National Planning Commission [MNPC], 2004). This study explored problem solving as one of the teaching methods used in Grade 10 Geography syllabuses as a response to such environmental issues/risks. Geography provides learners with an understanding of the issues and risks in their world that need to be addressed in order to improve the quality of their lives and health of their environment. This study focused on how environmental problems and problem-solving methods are presented in the Namibian Grade 10 Geography syllabus and how these are represented and implemented through teacher intentionality and practice. The theoretical framework for this study was informed by two theories namely risk society and social constructivism. This study was conducted at three schools in the Rundu circuit in the Kavango region and one teacher was involved in the study at each school. This study was conducted within an interpretive research tradition and was qualitative in nature. The study used document analysis, focus group discussion and classroom observation as data generation methods. The findings of the study reveal that the complexity of environmental issues is highlighted in the syllabus and in teachers’ intentionality and practice. The findings also show that a limited variety of teaching methods were used in problem solving strategies. The study also found that problem solving was influenced by different constructivist learning principles. The study further found that limited numbers of problem-solving steps were used in the process of problem solving. The study concludes by calling for further research into problem solving strategies. This can be done to empower Geography teachers to use more complex problem solving strategies to deepen problem solving and to engage problems in more depth.
- Full Text:
- Date Issued: 2016
The consumption and use of wild foods by children across a deforestation gradient in Zomba District, Malawi
- Authors: Maseko, Heather Nonhlanhla
- Date: 2016
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/3212 , vital:20392
- Description: Despite consensus on their significant nutritional value, wild foods are continually excluded from both food security statistics and economic values of natural resources. Though largely unexplored, there is evidence on the use of wild foods by children to supplement their diets and as a source of income. Children have knowledge on the gathering and hunting of selected wild food species and sources thereof. Wetlands, agro-ecosystems, natural forests, human landscapes and river systems remain important sources of wild food resources. The provision of and access to these resources are significantly affected by the interference and disruption to natural ecosystems. In Malawi, interference has been largely due to deforestation and land use change caused by an interplay of pressures from population growth for development and agricultural expansion. Against this background, the implications of deforestation and vegetation cover on the availability of wild foods and their access and use by children is largely unexplored. Through a comprehensive analysis of data collected from 150 children and 50 elderly men and women, the integration of Participatory Rural Appraisal (PRA) exercises and Geographic Information System (GIS), in the four sites of Mpheta, Mtuluma, Kasonga and Makombe in Zomba district, wild foods availability was established and their contribution to the nutritional status of children and households’ food security assessed. Study sites were identified along the deforestation gradient of Lake Chilwa, Zomba Mountain and Shire River basin with an additional focus on varying landscapes. One hundred and twenty species of wild foods were identified with greatest availability in areas of high vegetation cover and the lowest in areas of low vegetation cover, but with meaningful differences per wild food category. There was considerable reduction in the availability of wild foods with increasing deforestation; mainly wild game and fruits species and, in turn, decreased access of these by children. Nevertheless, small game, insects, other wild fruits and wild vegetables thrive well in agro-ecosystems and therefore were minimally affected by deforestation but largely by management practices of those systems and can be possibly improved through the promotion of agro-ecological farming systems. The research reveals that wild foods form an important component of the starch based diets of households from agricultural communities in the various landscapes. Besides securing the household’s food base, all children largely supplemented their diets with wild foods but with increased dependence by children from poorer households who are highly vulnerable to food insecurity. Access and use of wild foods was largely dependent on children’s knowledge, perceptions of the wild food and ease of access, with considerable variations due to gender and socio-cultural norms. Besides contributing to the nutritional status and food security, commercialisation of wild foods was common among children, hence providing them with an alternative livelihood strategy and in some cases only viable source of income.
- Full Text:
- Date Issued: 2016
- Authors: Maseko, Heather Nonhlanhla
- Date: 2016
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/3212 , vital:20392
- Description: Despite consensus on their significant nutritional value, wild foods are continually excluded from both food security statistics and economic values of natural resources. Though largely unexplored, there is evidence on the use of wild foods by children to supplement their diets and as a source of income. Children have knowledge on the gathering and hunting of selected wild food species and sources thereof. Wetlands, agro-ecosystems, natural forests, human landscapes and river systems remain important sources of wild food resources. The provision of and access to these resources are significantly affected by the interference and disruption to natural ecosystems. In Malawi, interference has been largely due to deforestation and land use change caused by an interplay of pressures from population growth for development and agricultural expansion. Against this background, the implications of deforestation and vegetation cover on the availability of wild foods and their access and use by children is largely unexplored. Through a comprehensive analysis of data collected from 150 children and 50 elderly men and women, the integration of Participatory Rural Appraisal (PRA) exercises and Geographic Information System (GIS), in the four sites of Mpheta, Mtuluma, Kasonga and Makombe in Zomba district, wild foods availability was established and their contribution to the nutritional status of children and households’ food security assessed. Study sites were identified along the deforestation gradient of Lake Chilwa, Zomba Mountain and Shire River basin with an additional focus on varying landscapes. One hundred and twenty species of wild foods were identified with greatest availability in areas of high vegetation cover and the lowest in areas of low vegetation cover, but with meaningful differences per wild food category. There was considerable reduction in the availability of wild foods with increasing deforestation; mainly wild game and fruits species and, in turn, decreased access of these by children. Nevertheless, small game, insects, other wild fruits and wild vegetables thrive well in agro-ecosystems and therefore were minimally affected by deforestation but largely by management practices of those systems and can be possibly improved through the promotion of agro-ecological farming systems. The research reveals that wild foods form an important component of the starch based diets of households from agricultural communities in the various landscapes. Besides securing the household’s food base, all children largely supplemented their diets with wild foods but with increased dependence by children from poorer households who are highly vulnerable to food insecurity. Access and use of wild foods was largely dependent on children’s knowledge, perceptions of the wild food and ease of access, with considerable variations due to gender and socio-cultural norms. Besides contributing to the nutritional status and food security, commercialisation of wild foods was common among children, hence providing them with an alternative livelihood strategy and in some cases only viable source of income.
- Full Text:
- Date Issued: 2016
Synthesis and exploration of resorcinol derivatives as Plasmodium falciparum Hsp90 inhibitors
- Authors: Umumararungu, Théoneste
- Date: 2016
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/717 , vital:19984
- Description: In this research project, we have synthesized a series of nine dimethyl ether resorcinol analogues of NMS-E973 (L-1) 38, a potent Hsp90 inhibitor. These analogues were chosen because they share the same pharmacophore with NMS-E973 (L-1) 38 and were thus expected to have a similar biological activity. Moreover, it is generally easier to synthesize the dimethyl ether resorcinol analogues of NMS-E973 (L-1) 38 as compared to their demethylated counterparts. Since other Hsp90 inhibitors such as geldanamycin 19 have demonstrated anti-plasmodial activity, we also expected our compounds to be Hsp90 inhibitors and to possess anti-plasmodial activity. However, our compounds were tested for growth inhibitory activity of Plasmodium falciparum and not for P. falciparum Hsp90 (PfHSP90) inhibitory activity. The synthesis involved a series of steps that led to the formation of the ester compound TU-011 (L-7) 43 that was then used as a precursor for different NMS-E973 (L-1) 38 analogues. The choice of analogues to be synthesized was dictated by binding affinity predictions obtained from molecular docking. The chosen synthetic analogues were active against chloroquine-sensitive Plasmodium falciparum (3D7 strain) in a Plasmodium lactate dehydrogenase assay and they were not generally cytotoxic to human cervical adenocarcinoma cell line HeLa. The most active of our compounds was TU-018 (L-103) 50 with an IC50 value of approximately 1.830 µM as compared to the standard, chloroquine, with an IC50 value of 0.01062 µM. Some of the compounds showed mild cytotoxicity towards HeLa cells with IC50 values higher than 25 µM as compared to the standard apoptosis inducer drug, emetine that had an IC50 value of 0.09948 µM. These results highlight the fact that the synthesized analogues are novel relatively non-toxic anti-plasmodial agents.
- Full Text:
- Date Issued: 2016
- Authors: Umumararungu, Théoneste
- Date: 2016
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/717 , vital:19984
- Description: In this research project, we have synthesized a series of nine dimethyl ether resorcinol analogues of NMS-E973 (L-1) 38, a potent Hsp90 inhibitor. These analogues were chosen because they share the same pharmacophore with NMS-E973 (L-1) 38 and were thus expected to have a similar biological activity. Moreover, it is generally easier to synthesize the dimethyl ether resorcinol analogues of NMS-E973 (L-1) 38 as compared to their demethylated counterparts. Since other Hsp90 inhibitors such as geldanamycin 19 have demonstrated anti-plasmodial activity, we also expected our compounds to be Hsp90 inhibitors and to possess anti-plasmodial activity. However, our compounds were tested for growth inhibitory activity of Plasmodium falciparum and not for P. falciparum Hsp90 (PfHSP90) inhibitory activity. The synthesis involved a series of steps that led to the formation of the ester compound TU-011 (L-7) 43 that was then used as a precursor for different NMS-E973 (L-1) 38 analogues. The choice of analogues to be synthesized was dictated by binding affinity predictions obtained from molecular docking. The chosen synthetic analogues were active against chloroquine-sensitive Plasmodium falciparum (3D7 strain) in a Plasmodium lactate dehydrogenase assay and they were not generally cytotoxic to human cervical adenocarcinoma cell line HeLa. The most active of our compounds was TU-018 (L-103) 50 with an IC50 value of approximately 1.830 µM as compared to the standard, chloroquine, with an IC50 value of 0.01062 µM. Some of the compounds showed mild cytotoxicity towards HeLa cells with IC50 values higher than 25 µM as compared to the standard apoptosis inducer drug, emetine that had an IC50 value of 0.09948 µM. These results highlight the fact that the synthesized analogues are novel relatively non-toxic anti-plasmodial agents.
- Full Text:
- Date Issued: 2016
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