Studies in the thiophenol mediated substitution and reductive dehalogenation of 3 bromoacetylcoumarins
- Authors: Magwenzi, Faith N
- Date: 2017
- Subjects: 3-bromoacetylcoumarins , Coumarins , Halogens -- Decontamination , Thiols , Plasmodium falciparum , Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/45769 , vital:25546
- Description: A previous study conducted by our group identified indolyl-3-ethanone-a-thioethers (2.1a and 2.1b) as non-toxic, nanomolar, in vitro inhibitors of Plasmodium falciparum. Since the coumarin scaffold is associated with numerous biologically active compounds including antiprotozoal, anti-viral, anti-bacterial, and anti-inflammatory agents we were prompted to investigate coumaryl-3-ethanone-a-thioethers (2.1c) inspired by the activity of 2.1a and 2.1b against P. falciparum. We proposed a three-step synthesis of our target compounds 2.1c. The first step involved the Knoevenagel synthesis of 3-acetyl coumarins (2.3.1a - e) followed by a selective a-bromination to yield 3-bromoacetyl coumarin (2.2a). The final proposed step involved the nucleophilic displacement of the bromine by appropriately substituted thiophenols in either the presence or absence of base (K2CO3). Our initial findings revealed an unexpected major reductive dehalogenation of 2.2a into 2.3.1a. Further investigation revealed a close relationship between the electron withdrawing or donating nature of the thiophenol substituents and the relative formation of nucleophilic substitution or reductive dehalogenation products. Desired thioether products were obtained in higher yields when thiophenol was substituted with electron donating groups i.e. more nucleophilic thiophenols, while conversely, electron withdrawing substituents (i.e. lowered nucleophilicity) resulted in an increase of reductive dehalogenation. Furthermore, these results were consistent when experiments were conducted using either 2 or 1.2 equivalents of thiophenols which was an important observation in the context of two previous studies, by Oki et. al. and Israel et. al. Oki proposed that dehalogenation of a-chloro carbonyls occurs via sequential nucleophilic displacement of a-thioethers, while the study of Israel concluded that the dehalogenation of a-iodo carbonyls occurred in a single discreet step. Finally, in an effort to enhance nucleophilic substitution through the addition of K2CO3, we observed a Robinson annulation resulting in previously undescribed C-8 thiophenol functionalised dibenzo[b,d]pyran-6-ones (3.4a - e). In the introduction to this thesis, we briefly summarise the utility of coumarins in medicinal chemistry and related fields. Chapter two describes the rationalisation of our original research question and a retrosynthetic analysis of our desired compounds, followed by an initial description of the unexpected reductive dehalogenation. Chapter 3, begins with a brief review of reductive dehalogenation of a-halocarbonyls, and is followed by an analysis and discussion of our results in the context of the studies by Israel et. al. and Oki et. al.
- Full Text:
- Authors: Magwenzi, Faith N
- Date: 2017
- Subjects: 3-bromoacetylcoumarins , Coumarins , Halogens -- Decontamination , Thiols , Plasmodium falciparum , Malaria -- Chemotherapy
- Language: English
- Type: Thesis , Masters , MPharm
- Identifier: http://hdl.handle.net/10962/45769 , vital:25546
- Description: A previous study conducted by our group identified indolyl-3-ethanone-a-thioethers (2.1a and 2.1b) as non-toxic, nanomolar, in vitro inhibitors of Plasmodium falciparum. Since the coumarin scaffold is associated with numerous biologically active compounds including antiprotozoal, anti-viral, anti-bacterial, and anti-inflammatory agents we were prompted to investigate coumaryl-3-ethanone-a-thioethers (2.1c) inspired by the activity of 2.1a and 2.1b against P. falciparum. We proposed a three-step synthesis of our target compounds 2.1c. The first step involved the Knoevenagel synthesis of 3-acetyl coumarins (2.3.1a - e) followed by a selective a-bromination to yield 3-bromoacetyl coumarin (2.2a). The final proposed step involved the nucleophilic displacement of the bromine by appropriately substituted thiophenols in either the presence or absence of base (K2CO3). Our initial findings revealed an unexpected major reductive dehalogenation of 2.2a into 2.3.1a. Further investigation revealed a close relationship between the electron withdrawing or donating nature of the thiophenol substituents and the relative formation of nucleophilic substitution or reductive dehalogenation products. Desired thioether products were obtained in higher yields when thiophenol was substituted with electron donating groups i.e. more nucleophilic thiophenols, while conversely, electron withdrawing substituents (i.e. lowered nucleophilicity) resulted in an increase of reductive dehalogenation. Furthermore, these results were consistent when experiments were conducted using either 2 or 1.2 equivalents of thiophenols which was an important observation in the context of two previous studies, by Oki et. al. and Israel et. al. Oki proposed that dehalogenation of a-chloro carbonyls occurs via sequential nucleophilic displacement of a-thioethers, while the study of Israel concluded that the dehalogenation of a-iodo carbonyls occurred in a single discreet step. Finally, in an effort to enhance nucleophilic substitution through the addition of K2CO3, we observed a Robinson annulation resulting in previously undescribed C-8 thiophenol functionalised dibenzo[b,d]pyran-6-ones (3.4a - e). In the introduction to this thesis, we briefly summarise the utility of coumarins in medicinal chemistry and related fields. Chapter two describes the rationalisation of our original research question and a retrosynthetic analysis of our desired compounds, followed by an initial description of the unexpected reductive dehalogenation. Chapter 3, begins with a brief review of reductive dehalogenation of a-halocarbonyls, and is followed by an analysis and discussion of our results in the context of the studies by Israel et. al. and Oki et. al.
- Full Text:
Studio photography as a contemporary genre: resisting historical and discursive legacy, forging new tropes
- Authors: Mukendi, J S T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/146533 , vital:38534 , https://www.ug.edu.gh/events/arts-council-african-studies-association-acasa-17th-triennial-symposium-august-8-%E2%80%93-13-2017
- Description: ACASA facilitates communication among scholars, teachers, students, artists, museum specialists, collectors, and all others interested in the arts of Africa and the African Diaspora. Its goals are to promote greater understanding of African material and expressive culture in all its forms, and to encourage contact and collaboration with African and Diaspora artists and scholars.
- Full Text:
- Authors: Mukendi, J S T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/146533 , vital:38534 , https://www.ug.edu.gh/events/arts-council-african-studies-association-acasa-17th-triennial-symposium-august-8-%E2%80%93-13-2017
- Description: ACASA facilitates communication among scholars, teachers, students, artists, museum specialists, collectors, and all others interested in the arts of Africa and the African Diaspora. Its goals are to promote greater understanding of African material and expressive culture in all its forms, and to encourage contact and collaboration with African and Diaspora artists and scholars.
- Full Text:
Study South Africa
- International Education Association of South Africa (IEASA), Quinlan, Orla
- Authors: International Education Association of South Africa (IEASA) , Quinlan, Orla
- Date: 2017
- Subjects: Education, Higher -- South Africa , Education and globalization -- South Africa Student mobility -- Africa International education -- South Africa Education, Higher -- International cooperation , Universities and colleges -- South Africa , Technical Institutes -- South Africa , Vocational guidance -- South Africa
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/64853 , vital:28620 , ISBN 9780620769662
- Description: [Editor's Letter]: Welcome to the seventeenth Study SA, compiled as IEASA celebrates its twentieth anniversary. Study SA is the South African publication that provides an overview of South African Higher Education issues and developments. This edition has a special Commemorative section, celebrating 20 years of IEASA, as well as the standard sections found in every issue of Study SA, consisting of Higher Education in Context, Features and Medical Aid and the updated profiles of the 26 public Higher Education Institutions. Universities South Africa, USAF, kindly provided partial funding for this edition of Study SA and we are delighted to include a message from the current CEO Dr Ahmed Bawa, a consistent supporter of internationalisation in Higher Education. We also have a message from the former Minister of Higher Education, Dr Blade Nzimande (2009-2017). A voluntary organisation supported by a small secretariat, IEASA is testament to a group of people who saw the need for an organisation to support the South African Higher Education’s re-entry and engagement with the rest of the world, once it became a democracy in 1994. This edition includes articles by two of the founding members: lEASA’s first President, Dr Roshun Kishun and its first Treasurer, Dr Derek Swemmer. Our sincere thanks to all the committed individuals in South African Higher education, who have kept IEASA going from strength to strength. Thilor Manikam, lEASA’s longest serving staffing member and the Office Manager has provided continuity and institutional memory over the best part of the twenty years. Guided by lEASA’s Constitution, Thilor has ensured that regardless of the change in the Management Council over the years, IEASA operations are impeccably managed and that IEASA has received an unqualified audit every year since its inception. In its history, IEASA has had seven Presidents: Dr Roshun Kishan, Ms Fazela Hanif, Mr David Ferrai, Ms Merle Hodges, Mr Lavern Samuels, Dr Nico Jooste and the current President Leolyn Jackson, whose term will run until the end of 2018, when the current President Elect, Ms Orla Quinlan will serve a two-year term from 2019-2020. IEASA has facilitated the development of a close knit community of practice in South Africa with members drawing on each other’s strengths and skills; inviting each other to our respective institutions to share knowledge, skills and ideas on appropriate internationalisation, within the South African context. More than that, we have become friends and have developed a collective responsibility to present and represent South African Higher Education to the rest of the world. Sadly, we lost three of our very dear colleagues and friends in recent years: Mr Len Mkhize, Mr Jimmy Ellis and Professor Stan Ridge. We pay tribute to the energy and joy they brought to IEASA in all their endeavours. They are missed. Others who have supported IEASA over the years include PWC, who have provided free audit services up to 2017, as a contribution to South Africa’s Higher Education; ABSA and the Medical Aid companies, who have provided sponsorship to IEASA. Finally, its volunteer Management Council, members of which serve two-year terms, with the possibility of being re-elected, and each one of our members who participate in and support IEASA activities and events. IEASA continued its work with the Department of Home Affairs (DHA) to clarify the visa application procedures, communicate the processes and to request interventions when visa processing is unduly delayed or if there are extenuating circumstances, which require intervention. IEASA and DHA have held one joint workshop with universities in 2016; a second was held following the IEASA 20th conference in August 2017 and an initial meeting called by USAF was held with DHA, HR Directors from universities and IEASA in late 2017. Visa Facilitation Services (VFS) have introduced a new mobile biometric service for campuses who do not have a VFS office in their locality. IEASA will continue to work on behalf of the international students and the rest of the international Higher Education community to improve the clarity of immigration requirements and to help overcome any difficulties faced. An article providing an update on progress is included in this edition. The international landscape has shifted enormously in recent years, where previously unquestioned democratic principles are being contested in some of the world’s most established democracies. lEASA’s 20th Anniversary Conference theme was “Advancing internationalisation: overcoming hostilities and building communities”. While in reflective and celebratory mode about the achievements of the last twenty years during the the Colloquium, the conference attendees switched mode and engaged in robust debates, about the current challenges in Higher Education including economic and financial challenges, xenophobia, the lack of equity in existing partnerships, institutional strategies, opportunities for engaging with partners interested in South African Higher Education. IEASA is cognisant of its responsibility to build capacity for the upcoming professionals in the sector and workshops on themes pertinent to the professionals in International Offices included immigration, partnerships and developing internationalisation strategy. , 17th Edition
- Full Text:
- Authors: International Education Association of South Africa (IEASA) , Quinlan, Orla
- Date: 2017
- Subjects: Education, Higher -- South Africa , Education and globalization -- South Africa Student mobility -- Africa International education -- South Africa Education, Higher -- International cooperation , Universities and colleges -- South Africa , Technical Institutes -- South Africa , Vocational guidance -- South Africa
- Language: English
- Type: text , book
- Identifier: http://hdl.handle.net/10962/64853 , vital:28620 , ISBN 9780620769662
- Description: [Editor's Letter]: Welcome to the seventeenth Study SA, compiled as IEASA celebrates its twentieth anniversary. Study SA is the South African publication that provides an overview of South African Higher Education issues and developments. This edition has a special Commemorative section, celebrating 20 years of IEASA, as well as the standard sections found in every issue of Study SA, consisting of Higher Education in Context, Features and Medical Aid and the updated profiles of the 26 public Higher Education Institutions. Universities South Africa, USAF, kindly provided partial funding for this edition of Study SA and we are delighted to include a message from the current CEO Dr Ahmed Bawa, a consistent supporter of internationalisation in Higher Education. We also have a message from the former Minister of Higher Education, Dr Blade Nzimande (2009-2017). A voluntary organisation supported by a small secretariat, IEASA is testament to a group of people who saw the need for an organisation to support the South African Higher Education’s re-entry and engagement with the rest of the world, once it became a democracy in 1994. This edition includes articles by two of the founding members: lEASA’s first President, Dr Roshun Kishun and its first Treasurer, Dr Derek Swemmer. Our sincere thanks to all the committed individuals in South African Higher education, who have kept IEASA going from strength to strength. Thilor Manikam, lEASA’s longest serving staffing member and the Office Manager has provided continuity and institutional memory over the best part of the twenty years. Guided by lEASA’s Constitution, Thilor has ensured that regardless of the change in the Management Council over the years, IEASA operations are impeccably managed and that IEASA has received an unqualified audit every year since its inception. In its history, IEASA has had seven Presidents: Dr Roshun Kishan, Ms Fazela Hanif, Mr David Ferrai, Ms Merle Hodges, Mr Lavern Samuels, Dr Nico Jooste and the current President Leolyn Jackson, whose term will run until the end of 2018, when the current President Elect, Ms Orla Quinlan will serve a two-year term from 2019-2020. IEASA has facilitated the development of a close knit community of practice in South Africa with members drawing on each other’s strengths and skills; inviting each other to our respective institutions to share knowledge, skills and ideas on appropriate internationalisation, within the South African context. More than that, we have become friends and have developed a collective responsibility to present and represent South African Higher Education to the rest of the world. Sadly, we lost three of our very dear colleagues and friends in recent years: Mr Len Mkhize, Mr Jimmy Ellis and Professor Stan Ridge. We pay tribute to the energy and joy they brought to IEASA in all their endeavours. They are missed. Others who have supported IEASA over the years include PWC, who have provided free audit services up to 2017, as a contribution to South Africa’s Higher Education; ABSA and the Medical Aid companies, who have provided sponsorship to IEASA. Finally, its volunteer Management Council, members of which serve two-year terms, with the possibility of being re-elected, and each one of our members who participate in and support IEASA activities and events. IEASA continued its work with the Department of Home Affairs (DHA) to clarify the visa application procedures, communicate the processes and to request interventions when visa processing is unduly delayed or if there are extenuating circumstances, which require intervention. IEASA and DHA have held one joint workshop with universities in 2016; a second was held following the IEASA 20th conference in August 2017 and an initial meeting called by USAF was held with DHA, HR Directors from universities and IEASA in late 2017. Visa Facilitation Services (VFS) have introduced a new mobile biometric service for campuses who do not have a VFS office in their locality. IEASA will continue to work on behalf of the international students and the rest of the international Higher Education community to improve the clarity of immigration requirements and to help overcome any difficulties faced. An article providing an update on progress is included in this edition. The international landscape has shifted enormously in recent years, where previously unquestioned democratic principles are being contested in some of the world’s most established democracies. lEASA’s 20th Anniversary Conference theme was “Advancing internationalisation: overcoming hostilities and building communities”. While in reflective and celebratory mode about the achievements of the last twenty years during the the Colloquium, the conference attendees switched mode and engaged in robust debates, about the current challenges in Higher Education including economic and financial challenges, xenophobia, the lack of equity in existing partnerships, institutional strategies, opportunities for engaging with partners interested in South African Higher Education. IEASA is cognisant of its responsibility to build capacity for the upcoming professionals in the sector and workshops on themes pertinent to the professionals in International Offices included immigration, partnerships and developing internationalisation strategy. , 17th Edition
- Full Text:
Subjectivity and social resistance: a theoretical analysis of the Matrix Trilogy
- Authors: Jamal, Ahmad
- Date: 2017
- Subjects: Matrix (Motion picture) , Matrix reloaded (Motion picture) , Matrix revolution (Motion picture) Baudrillard, Jean, 1929-2007. Simulacres et Simulation , Science fiction -- Philosophy , Mass media -- Social aspects , Culture in motion pictures , Dystopian films
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/7011 , vital:21209
- Description: The Matrix (1999) is a science-fiction film that successfully bridges modern cinematic action sequences with philosophical parables. It recalls the tradition of philosophical elaboration through science-fiction narratives; a tradition that has existed since the time of Plato. This study aims to bridge the divide between philosophy and psychology by using a theoretical analysis to discuss and explore the ideas of social thinkers (featured in the Matrix Trilogy) and critically analyse them alongside established psychological theories. More specifically, this study provides an in-depth and critical exploration of the ways in which the philosophical works of Jean Baudrillard and Karl Marx, and the widely used and recognised psychological perspectives on human development, cognition and learning offered by both Urie Broffenbrenner and Jean Piaget to simultaneously elucidate a model of human subjectivity and development in today's techno- consumerist society with specific attention to critical resistance. This study suggests that with the rise of the internet and modern communication media; sociocultural and political issues that Broffenbrenner conceptualised as existing in the macrosystem, now have a presence in the microsystem, and correspond to Broffenbrenner's requirements as to what constitutes a proximal process. These processes, according to Broffenbrenner, have the most longstanding effects on our development and contribute the most to our personality. This study also argues that the pre-operational stage and the process of symbolisation both of which Piaget identified are important phases in the child's life that see the accrual and development of signs and discourses. These signs and discourses then contribute to the development of our mind's cognitive structures which Piaget called schema. These structures are developed as we grow and help us make sense of the world by processing information and organising our experiences. This would mean that we perceive and interpret our world through ideologically shaped mental structures. These findings stress the importance of ideological influences and their impact on development and hearken more closely towards ideas about the presence and the effects of ideology by thinkers like Plato and Marx, as well as the dystopian futures explored in science-fiction media like the Matrix Trilogy, George Orwell's 1984 (1948) and Aldous Huxley's A Brave New World (1932), and also the options for critical social resistance explored in the narratives and heroic deeds of these books and their characters.
- Full Text:
- Authors: Jamal, Ahmad
- Date: 2017
- Subjects: Matrix (Motion picture) , Matrix reloaded (Motion picture) , Matrix revolution (Motion picture) Baudrillard, Jean, 1929-2007. Simulacres et Simulation , Science fiction -- Philosophy , Mass media -- Social aspects , Culture in motion pictures , Dystopian films
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/7011 , vital:21209
- Description: The Matrix (1999) is a science-fiction film that successfully bridges modern cinematic action sequences with philosophical parables. It recalls the tradition of philosophical elaboration through science-fiction narratives; a tradition that has existed since the time of Plato. This study aims to bridge the divide between philosophy and psychology by using a theoretical analysis to discuss and explore the ideas of social thinkers (featured in the Matrix Trilogy) and critically analyse them alongside established psychological theories. More specifically, this study provides an in-depth and critical exploration of the ways in which the philosophical works of Jean Baudrillard and Karl Marx, and the widely used and recognised psychological perspectives on human development, cognition and learning offered by both Urie Broffenbrenner and Jean Piaget to simultaneously elucidate a model of human subjectivity and development in today's techno- consumerist society with specific attention to critical resistance. This study suggests that with the rise of the internet and modern communication media; sociocultural and political issues that Broffenbrenner conceptualised as existing in the macrosystem, now have a presence in the microsystem, and correspond to Broffenbrenner's requirements as to what constitutes a proximal process. These processes, according to Broffenbrenner, have the most longstanding effects on our development and contribute the most to our personality. This study also argues that the pre-operational stage and the process of symbolisation both of which Piaget identified are important phases in the child's life that see the accrual and development of signs and discourses. These signs and discourses then contribute to the development of our mind's cognitive structures which Piaget called schema. These structures are developed as we grow and help us make sense of the world by processing information and organising our experiences. This would mean that we perceive and interpret our world through ideologically shaped mental structures. These findings stress the importance of ideological influences and their impact on development and hearken more closely towards ideas about the presence and the effects of ideology by thinkers like Plato and Marx, as well as the dystopian futures explored in science-fiction media like the Matrix Trilogy, George Orwell's 1984 (1948) and Aldous Huxley's A Brave New World (1932), and also the options for critical social resistance explored in the narratives and heroic deeds of these books and their characters.
- Full Text:
Suspense, the serious and the superman:
- Authors: Western, Rat
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/147726 , vital:38664 , https://doi.org/10.1080/00043389.2012.11877164
- Description: When considering what to do with one’s Friday night, probably very few people would consider a two-hour formal lecture a top priority. But this is a Friday night in Grahamstown, where novelty in leisure and entertainment choices, outside of festival time, is a rarity. It is therefore unsurprising that, on the evening of 11 November 2011, the Rhodes Box Theatre is packed by 7 pm with a variety of students, academics, members of the local alternative scene and the general public.
- Full Text:
- Authors: Western, Rat
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/147726 , vital:38664 , https://doi.org/10.1080/00043389.2012.11877164
- Description: When considering what to do with one’s Friday night, probably very few people would consider a two-hour formal lecture a top priority. But this is a Friday night in Grahamstown, where novelty in leisure and entertainment choices, outside of festival time, is a rarity. It is therefore unsurprising that, on the evening of 11 November 2011, the Rhodes Box Theatre is packed by 7 pm with a variety of students, academics, members of the local alternative scene and the general public.
- Full Text:
Sustainable tourism opportunities for Mauritius
- Authors: Ternel, Maeva
- Date: 2017
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10962/6118 , vital:21046
- Description: Sustainable Tourism (ST) integrates governance, economic, socio-cultural and environmental dimensions of tourism in tourism development and management. Growing Environmental, Social and Governance (ESG) concerns suggest that traditionally, tourism tends to corrupt the very resources it needs to thrive, and thus its sustainability over the long haul has become of general concern. However, despite the vast and extensive literature dedicated to ST, including preeminent journals providing both a theoretical base and reliable empirical evidence to the subject, the concept of sustainability in tourism remains somehow at its embryonic stage, especially in the case of a small island developing state (SIDS). The research occurred within the context of the destination (Mauritius), with however, a focus on five sizeable Mauritian hotel groups. With tourism being one of the pillars of the Mauritian economy, this research intended to explore the different repercussions of such an industry. The aim of the research was to determine to what extent tourism’s operations and development, was appropriately managed in Mauritius by assessing the country’s current tourism situation relating to sustainability and identifying priority areas for intervention. This, was done using different tools, including the United Nations World Tourism Organisation's framework, the Global Sustainable Tourism Council's guidelines and the Sustainable Tourism Attitude Scale. The contribution this research intended to make was to suggest sustainable tourism opportunities and make recommendations for the tourism sector and its stakeholders for the island of Mauritius. Overall, the research concluded that despite the increased importance of ST, the need for Managed Tourism (MT) and the formulation of general principles and guidelines, tourism governance; poverty reduction; and the sustainability of the natural and cultural environment were identified as areas of particular need and should be considered with high priority for intervention/action.
- Full Text:
- Authors: Ternel, Maeva
- Date: 2017
- Language: English
- Type: Thesis , Masters , MBA
- Identifier: http://hdl.handle.net/10962/6118 , vital:21046
- Description: Sustainable Tourism (ST) integrates governance, economic, socio-cultural and environmental dimensions of tourism in tourism development and management. Growing Environmental, Social and Governance (ESG) concerns suggest that traditionally, tourism tends to corrupt the very resources it needs to thrive, and thus its sustainability over the long haul has become of general concern. However, despite the vast and extensive literature dedicated to ST, including preeminent journals providing both a theoretical base and reliable empirical evidence to the subject, the concept of sustainability in tourism remains somehow at its embryonic stage, especially in the case of a small island developing state (SIDS). The research occurred within the context of the destination (Mauritius), with however, a focus on five sizeable Mauritian hotel groups. With tourism being one of the pillars of the Mauritian economy, this research intended to explore the different repercussions of such an industry. The aim of the research was to determine to what extent tourism’s operations and development, was appropriately managed in Mauritius by assessing the country’s current tourism situation relating to sustainability and identifying priority areas for intervention. This, was done using different tools, including the United Nations World Tourism Organisation's framework, the Global Sustainable Tourism Council's guidelines and the Sustainable Tourism Attitude Scale. The contribution this research intended to make was to suggest sustainable tourism opportunities and make recommendations for the tourism sector and its stakeholders for the island of Mauritius. Overall, the research concluded that despite the increased importance of ST, the need for Managed Tourism (MT) and the formulation of general principles and guidelines, tourism governance; poverty reduction; and the sustainability of the natural and cultural environment were identified as areas of particular need and should be considered with high priority for intervention/action.
- Full Text:
Synthesis and anti-parasitic activity of C-benzylated (N-arylcarbamoyl) alkylphosphonate esters
- Adeyemi, Christiana Modupe, Isaacs, Michelle, Mnkandhla, Dumisani, Krause, Rui W M, Klein, Rosalyn, Hoppe, Heinrich C, Lobb, Kevin A, Kaye, Perry T
- Authors: Adeyemi, Christiana Modupe , Isaacs, Michelle , Mnkandhla, Dumisani , Krause, Rui W M , Klein, Rosalyn , Hoppe, Heinrich C , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125641 , vital:35803 , https://doi.org/10.1016/j.tet.2017.01.045
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Authors: Adeyemi, Christiana Modupe , Isaacs, Michelle , Mnkandhla, Dumisani , Krause, Rui W M , Klein, Rosalyn , Hoppe, Heinrich C , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/125641 , vital:35803 , https://doi.org/10.1016/j.tet.2017.01.045
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl)phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
Synthesis and anti-parasitic activity of C-benzylated (N-arylcarbamoyl) alkylphosphonate esters
- Adeyemi, Christiana M, Isaacs, Michelle, Mnkandhla, Dumisani, Klein, Rosalyn, Hoppe, Heinrich C, Krause, Rui W M, Lobb, Kevin A, Kaye, Perry T
- Authors: Adeyemi, Christiana M , Isaacs, Michelle , Mnkandhla, Dumisani , Klein, Rosalyn , Hoppe, Heinrich C , Krause, Rui W M , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/477661 , vital:78109 , xlink:href="https://doi.org/10.1016/j.tet.2017.01.045"
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl) phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
- Authors: Adeyemi, Christiana M , Isaacs, Michelle , Mnkandhla, Dumisani , Klein, Rosalyn , Hoppe, Heinrich C , Krause, Rui W M , Lobb, Kevin A , Kaye, Perry T
- Date: 2017
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/477661 , vital:78109 , xlink:href="https://doi.org/10.1016/j.tet.2017.01.045"
- Description: Unexpected substituent-dependent regioselectivty challenges in the synthesis of C-benzylated (N-arylcarbamoyl) phosphonate esters have been resolved. The C-benzylated N-furfurylcarbamoyl derivative showed low micromolar PfLDH inhibition, while one of the C-benzylated N-arylcarbamoyl analogues was active against Nagana Trypanosoma brucei parasites which are responsible for African trypanosomiasis in cattle.
- Full Text:
Synthesis and bioassay of rationally designed DXR inhibitors as potential antimalarial lead compounds
- Authors: Nokalipa, Iviwe Cwaita
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4888 , vital:20740
- Description: Globally, the eradication of malaria has been challenging due to the problem of resistance that past and currently available drugs exhibit. This is exacerbated by the inherent need for anti-malarial drugs to be affordable to the poverty-stricken majority that is primarily affected by this burden. This research has focused on the development of potential inhibitors of 1-deoxy-D- xylulose-5 phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate- independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate into 2-C- methyl-D-erithrytol 4-phosphate. This enzyme has been determined to be a target for the development of novel antimalarial agents and extensive molecular modelling has been undertaken to develop inhibitors that fit into the DXR active site. The in silico docking data have been used to inform the design and synthesis of various N-benzyl-substituted phosphoramidate ligands that were determined to have potential as novel substrate mimics of fosmidomycin, a known DXR inhibitor. Synthesis of the N-benzyl-substituted phosphoramidate ligands involved a nine-step sequence commencing from diethyl phosphoramidate. In all, some 40 compounds have been prepared, some of them new, and were fully characterized using NMR. Attention has also been given to the mass spectrometric fragmentation patterns exhibited by selected intermediates. Four of the final products were evaluated for in vitro antimalarial activity using a PLDH assay and exhibited IC50 values < 100 µM.
- Full Text:
- Authors: Nokalipa, Iviwe Cwaita
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4888 , vital:20740
- Description: Globally, the eradication of malaria has been challenging due to the problem of resistance that past and currently available drugs exhibit. This is exacerbated by the inherent need for anti-malarial drugs to be affordable to the poverty-stricken majority that is primarily affected by this burden. This research has focused on the development of potential inhibitors of 1-deoxy-D- xylulose-5 phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate- independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate into 2-C- methyl-D-erithrytol 4-phosphate. This enzyme has been determined to be a target for the development of novel antimalarial agents and extensive molecular modelling has been undertaken to develop inhibitors that fit into the DXR active site. The in silico docking data have been used to inform the design and synthesis of various N-benzyl-substituted phosphoramidate ligands that were determined to have potential as novel substrate mimics of fosmidomycin, a known DXR inhibitor. Synthesis of the N-benzyl-substituted phosphoramidate ligands involved a nine-step sequence commencing from diethyl phosphoramidate. In all, some 40 compounds have been prepared, some of them new, and were fully characterized using NMR. Attention has also been given to the mass spectrometric fragmentation patterns exhibited by selected intermediates. Four of the final products were evaluated for in vitro antimalarial activity using a PLDH assay and exhibited IC50 values < 100 µM.
- Full Text:
Synthesis and biological evaluation of anti-HIV-I integrase agents
- Jesumoroti, Omobolanle Janet
- Authors: Jesumoroti, Omobolanle Janet
- Date: 2017
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/59215 , vital:27479
- Description: Expected release date-April 2019
- Full Text:
- Authors: Jesumoroti, Omobolanle Janet
- Date: 2017
- Language: English
- Type: text , Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/59215 , vital:27479
- Description: Expected release date-April 2019
- Full Text:
Synthesis and evaluation of arylpyrrole-chalcone hybrids as antiplasmodial and antitrypanosomal agents
- Authors: Zulu, Ayanda Ignatia
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65268 , vital:28716
- Description: Expected release date-May 2019
- Full Text:
- Authors: Zulu, Ayanda Ignatia
- Date: 2017
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/65268 , vital:28716
- Description: Expected release date-May 2019
- Full Text:
Synthesis and photophysical studies of asymmetric zinc phthalocyanine–magnetic nanoparticle conjugates
- Matlou, Gauta G, Kobayashi, Nagao, Kimura, Mutsumi, Nyokong, Tebello
- Authors: Matlou, Gauta G , Kobayashi, Nagao , Kimura, Mutsumi , Nyokong, Tebello
- Date: 2017
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/232895 , vital:50036 , xlink:href="https://doi.org/10.1039/C7NJ01716B"
- Description: This work reports on the synthesis and amide bond linkage of carboxylic acid functionalized asymmetric zinc phthalocyanine (ZnPc) complexes to amino magnetic nanoparticles (AMNPs). The work further compares the photophysical and photochemical parameters of the Pc complexes alone with those linked to form ZnPc–AMNPs with further relation to the type of the spacer between the Pc and the AMNPs. Infrared spectroscopy confirmed the presence of the amide bond formed between the Pc complexes and the AMNPs. The triplet quantum yields ranged from 0.62 to 0.87. However, low singlet oxygen quantum yields were obtained due to competing pathways and the insufficient energy transfer from the excited triplet state of the ZnPc molecules to the molecular oxygen.
- Full Text:
- Authors: Matlou, Gauta G , Kobayashi, Nagao , Kimura, Mutsumi , Nyokong, Tebello
- Date: 2017
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/232895 , vital:50036 , xlink:href="https://doi.org/10.1039/C7NJ01716B"
- Description: This work reports on the synthesis and amide bond linkage of carboxylic acid functionalized asymmetric zinc phthalocyanine (ZnPc) complexes to amino magnetic nanoparticles (AMNPs). The work further compares the photophysical and photochemical parameters of the Pc complexes alone with those linked to form ZnPc–AMNPs with further relation to the type of the spacer between the Pc and the AMNPs. Infrared spectroscopy confirmed the presence of the amide bond formed between the Pc complexes and the AMNPs. The triplet quantum yields ranged from 0.62 to 0.87. However, low singlet oxygen quantum yields were obtained due to competing pathways and the insufficient energy transfer from the excited triplet state of the ZnPc molecules to the molecular oxygen.
- Full Text:
Synthesis and photophysical studies of crown ether-bodipy dyes and the fabrication of bodipy embedded fluorescent nanofibers
- Authors: Stone, Justin
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4953 , vital:20746
- Description: This study has three major objectives: 1) to synthesize a series of structurally related BODIPY dyes, 2) to fabricate BODIPY embedded electrospun nanofibers, and 3) to investigate and characterize the photophysical properties of all synthesized BODIPY dyes with a special focus on their ability to generate singlet oxygen. This thesis first explores the acid catalysed condensation reaction to produce two structurally analogous meso-substituted BODIPY dyes based on cuminaldehyde and 4-dimethylaminobenzaldehdye. In order to enhance the rate of ISC and promote the generation of reactive oxygen species bromine atoms were then attached to the BODIPY 2,6-positions. These BODIPY dyes were then embedded in a polystyrene solution and electrospun into nanofibers. The resulting nanofibers were found to be highly fluorescent, but were no longer able to generate singlet oxygen. Ion-sensitive BODIPYs were prepared from the dibrominated BODIPY dyes by employing a modified Knoevenagel condensation reaction to form a styryl bond with 4’-formylbenzo-15-crown-5 at the 3,5-position of the BODIPY core. Changes in the morphology and position of the absorption and emission spectra of these crown ether-styryl BODIPY dyes were observed in the presence of sodium ions. These results imply that crown ether-substituted BODIPY dyes could function as ion sensors.
- Full Text:
- Authors: Stone, Justin
- Date: 2017
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4953 , vital:20746
- Description: This study has three major objectives: 1) to synthesize a series of structurally related BODIPY dyes, 2) to fabricate BODIPY embedded electrospun nanofibers, and 3) to investigate and characterize the photophysical properties of all synthesized BODIPY dyes with a special focus on their ability to generate singlet oxygen. This thesis first explores the acid catalysed condensation reaction to produce two structurally analogous meso-substituted BODIPY dyes based on cuminaldehyde and 4-dimethylaminobenzaldehdye. In order to enhance the rate of ISC and promote the generation of reactive oxygen species bromine atoms were then attached to the BODIPY 2,6-positions. These BODIPY dyes were then embedded in a polystyrene solution and electrospun into nanofibers. The resulting nanofibers were found to be highly fluorescent, but were no longer able to generate singlet oxygen. Ion-sensitive BODIPYs were prepared from the dibrominated BODIPY dyes by employing a modified Knoevenagel condensation reaction to form a styryl bond with 4’-formylbenzo-15-crown-5 at the 3,5-position of the BODIPY core. Changes in the morphology and position of the absorption and emission spectra of these crown ether-styryl BODIPY dyes were observed in the presence of sodium ions. These results imply that crown ether-substituted BODIPY dyes could function as ion sensors.
- Full Text:
Synthesis and physicochemical evaluation of a series of boron dipyrromethene dye derivatives for potential utility in antimicrobial photodynamic therapy and nonlinear optics
- Authors: Kubheka, Gugu Patience
- Date: 2017
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Nonlinear optics , BODIPY
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4776 , vital:20723
- Description: A series of new BODIPY dye derivatives have been synthesized and characterized using various characterization tools such as 1H-NMR, MALDI-TOF mass spectrometry, FT-IR, UV-visible spectrophotometry and elemental analysis. The aniline-substituted BODIPY derivative was further coordinated with gold nanorods and the characterization was achieved by transmission electron microscopy (TEM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS).In addition to this dye, quaternized BODIPY dyes were also synthesized and investigated for their potential utility as photosentitizers in antimicrobial photodynamic therapy (APDT).BODIPY dyes with pyrene substituted styryl groups were embedded in polymer thin film using poly(bisphenol A carbonate) (PBC) to study their optical limiting properties. The optical limiting values of these BODIPY dyes once embedded in thin films were found to be greatly improved and the limiting intensityof each film was well below the maximum threshold which is set to be 0.95 J.cm-². The physicochemical properties and NLO parameters of all of the synthesized dyes were investigated.
- Full Text:
- Authors: Kubheka, Gugu Patience
- Date: 2017
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Nonlinear optics , BODIPY
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4776 , vital:20723
- Description: A series of new BODIPY dye derivatives have been synthesized and characterized using various characterization tools such as 1H-NMR, MALDI-TOF mass spectrometry, FT-IR, UV-visible spectrophotometry and elemental analysis. The aniline-substituted BODIPY derivative was further coordinated with gold nanorods and the characterization was achieved by transmission electron microscopy (TEM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS).In addition to this dye, quaternized BODIPY dyes were also synthesized and investigated for their potential utility as photosentitizers in antimicrobial photodynamic therapy (APDT).BODIPY dyes with pyrene substituted styryl groups were embedded in polymer thin film using poly(bisphenol A carbonate) (PBC) to study their optical limiting properties. The optical limiting values of these BODIPY dyes once embedded in thin films were found to be greatly improved and the limiting intensityof each film was well below the maximum threshold which is set to be 0.95 J.cm-². The physicochemical properties and NLO parameters of all of the synthesized dyes were investigated.
- Full Text:
Synthesis of indium and lead phthalocyanine as photocatalysts for photodynamic antimicrobial chemotherapy and photo-oxidation of pollutants
- Authors: Oluwole, Oluyinka David
- Date: 2017
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/5293 , vital:20805
- Full Text:
- Authors: Oluwole, Oluyinka David
- Date: 2017
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/5293 , vital:20805
- Full Text:
Synthesis of indium and lead phthalocyanine as photocatalysts for photodynamic antimicrobial chemotherapy and photo-oxidation of pollutants
- Authors: Osifeko, Olawale L
- Date: 2017
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/5221 , vital:20790
- Description: This thesis explores the synthesis of metallophthalocyanines as potential photosensitizers for application in photodynamic antimicrobial chemotherapy and phototransformation of environmental pollutants. The metallophthalocyanines containing amino substituent were conjugated with magnetic nanoparticle and semiconductor quantum dots via an amide bond and by chemisorption onto gold nanoparticles surface. Techniques such as time-resolved fluorescence measurements, transmission electron microscopy, X-ray photoelectron spectroscopy (XPS), elemental analysis, fourier transform infrared (FTIR), nuclear magnetic resonance (¹H, ¹³C, and cozy of symmetrical phthalocyanine), electronic spectroscopy, as well as mass spectroscopy were employed to characterize all metallophthalocyanines. Quarternized pyridyloxy substituted phthalocyanine and asymmetric (AB3) metallophthalocyanines were embedded in electrospun polystyrene fiber. General trends are described for quantum yields of fluorescence, triplet, singlet oxygen and photodegradation as well as lifetimes of fluorescence and triplet state of the compounds. There is an increase in triplet quantum yield for Pcs in the presence of gold nanoparticles (AuNPs) and semiconductor quantum dots (QDs), but not in the presence of magnetic nanoparticles (MNPs). Photodynamic inactivation of Escherichia coli with the quarternized photosensitizers at low concentrations totally inactivate the bacteria compared to non-charged photosensitiser. Also, a similar trend was observed for the magnetic nanoparticles conjugates. Photooxidations of bisphenol A and 4-chlorophenol were carried out in this study using two asymmetric Indium(III) phthalocyanines photosensitizers. The photooxidation reactions were compared with those of a symmetrical indium(III) phthalocyanines containing four quaternized 4-pyridyloxy substituents. The complexes were embedded in electrospun polystyrene fiber for heterogeneous photocatalysis. The immobilized photosensitizers possess good singlet oxygen generation potentials in aqueous media. The asymmetrical phthalocyanine containing 4-pyridylsulfanyl and one aminophenoxy showed the best photocatalytic behavior.
- Full Text:
- Authors: Osifeko, Olawale L
- Date: 2017
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/5221 , vital:20790
- Description: This thesis explores the synthesis of metallophthalocyanines as potential photosensitizers for application in photodynamic antimicrobial chemotherapy and phototransformation of environmental pollutants. The metallophthalocyanines containing amino substituent were conjugated with magnetic nanoparticle and semiconductor quantum dots via an amide bond and by chemisorption onto gold nanoparticles surface. Techniques such as time-resolved fluorescence measurements, transmission electron microscopy, X-ray photoelectron spectroscopy (XPS), elemental analysis, fourier transform infrared (FTIR), nuclear magnetic resonance (¹H, ¹³C, and cozy of symmetrical phthalocyanine), electronic spectroscopy, as well as mass spectroscopy were employed to characterize all metallophthalocyanines. Quarternized pyridyloxy substituted phthalocyanine and asymmetric (AB3) metallophthalocyanines were embedded in electrospun polystyrene fiber. General trends are described for quantum yields of fluorescence, triplet, singlet oxygen and photodegradation as well as lifetimes of fluorescence and triplet state of the compounds. There is an increase in triplet quantum yield for Pcs in the presence of gold nanoparticles (AuNPs) and semiconductor quantum dots (QDs), but not in the presence of magnetic nanoparticles (MNPs). Photodynamic inactivation of Escherichia coli with the quarternized photosensitizers at low concentrations totally inactivate the bacteria compared to non-charged photosensitiser. Also, a similar trend was observed for the magnetic nanoparticles conjugates. Photooxidations of bisphenol A and 4-chlorophenol were carried out in this study using two asymmetric Indium(III) phthalocyanines photosensitizers. The photooxidation reactions were compared with those of a symmetrical indium(III) phthalocyanines containing four quaternized 4-pyridyloxy substituents. The complexes were embedded in electrospun polystyrene fiber for heterogeneous photocatalysis. The immobilized photosensitizers possess good singlet oxygen generation potentials in aqueous media. The asymmetrical phthalocyanine containing 4-pyridylsulfanyl and one aminophenoxy showed the best photocatalytic behavior.
- Full Text:
Synthesis of silver nanoparticles from a Desmodium adscendens extract and its antibacterial evaluation on wound dressing material
- Lakkakula, Jaya R, Ndinteh, Derek T, van Vuuren, Sandy F, Olivier, Denise K, Krause, Rui W M
- Authors: Lakkakula, Jaya R , Ndinteh, Derek T , van Vuuren, Sandy F , Olivier, Denise K , Krause, Rui W M
- Date: 2017
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195025 , vital:45520 , xlink:href="https://doi.org/10.1049/iet-nbt.2017.0084"
- Description: The one-pot synthesis of silver nanoparticles (AgNPs) using the medium-polar extract of Desmodium adscendens (Sw.) DC. is presented here as an alternative synthesis of metal NPs. Characterisation of the formed NPs showed polydispersed AgNPs ranging from 15 to 100 nm where the concentration of metal ions was found to play a role in the size and shape of the prepared NPs. It could be established that the flavonoids, saponins, and alkaloids present in the extract acted as both reducing and stabilising agents during the formation of the capped metal NPs. This means of NP synthesis was also employed during the in situ immobilisation of AgNPs on gauze and plaster. An evaluation of the antibacterial activity of the medium-polar D. adscendens extract, AgNPs suspended in solution, and the immobilised AgNPs against Staphylococcus aureus (ATCC 25923), Bacillus cereus (ATCC 11778), and Escherichia coli (ATCC 25922) showed high efficacy against the latter in particular. This suggests that gauze, dilute silver nitrate solutions, and D. adscendens extract could be used successfully in the simple in situ preparation of effective antibacterial wound dressings.
- Full Text:
- Authors: Lakkakula, Jaya R , Ndinteh, Derek T , van Vuuren, Sandy F , Olivier, Denise K , Krause, Rui W M
- Date: 2017
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/195025 , vital:45520 , xlink:href="https://doi.org/10.1049/iet-nbt.2017.0084"
- Description: The one-pot synthesis of silver nanoparticles (AgNPs) using the medium-polar extract of Desmodium adscendens (Sw.) DC. is presented here as an alternative synthesis of metal NPs. Characterisation of the formed NPs showed polydispersed AgNPs ranging from 15 to 100 nm where the concentration of metal ions was found to play a role in the size and shape of the prepared NPs. It could be established that the flavonoids, saponins, and alkaloids present in the extract acted as both reducing and stabilising agents during the formation of the capped metal NPs. This means of NP synthesis was also employed during the in situ immobilisation of AgNPs on gauze and plaster. An evaluation of the antibacterial activity of the medium-polar D. adscendens extract, AgNPs suspended in solution, and the immobilised AgNPs against Staphylococcus aureus (ATCC 25923), Bacillus cereus (ATCC 11778), and Escherichia coli (ATCC 25922) showed high efficacy against the latter in particular. This suggests that gauze, dilute silver nitrate solutions, and D. adscendens extract could be used successfully in the simple in situ preparation of effective antibacterial wound dressings.
- Full Text:
Synthesis, characterisation and evaluation of benzoxaborole-based hybrids as antiplasmodial agents
- Authors: Gumbo, Maureen
- Date: 2017
- Subjects: Malaria Chemotherapy , Antimalarials , Boron compounds , Drug resistance , Plasmodium falciparum , Drug development
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59193 , vital:27456
- Description: Malaria is a mosquito-borne disease, which continues to pose a threat to the entire humanity. About 40% of the world population is estimated to be at risk of infections by malaria. Despite efforts undertaken by scientific community, government entities and international organizations, malaria is still rampant. The major problem is drug resistance, where the Plasmodium spp have over the past decades developed drug resistance against available drugs. In order to counter this problem, novel antimalarial drugs that are efficacious and with novel mode of action are of great necessity. Benzoxaborole derivatives have been shown to exhibit promising antimalarial activity against Plasmodium falciparum strains. Previous studies reported on the compounds such as 6-(2- (alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles, which showed good antimalarial activity against both W7 and 3D7 strains without significant toxicity. On the other hand, chloroquine (CQ) and cinnamic acids have a wide variety of biological activity including antimalarial activity. Herein, a hybridisation strategy was employed to synthesise new CQ-benzoxaborole and cinnamoyl-benzoxaborole hybrids. CQ-Benzoxaborole 2.12a-c and cinnamoylbenzoxaborole 2.11a-g hydrid molecules were synthesised in low to good yields. Their structural identities were confirmed using conventional spectroscopic techniques (1H and 13C NMR, and mass spectrometry). CQ-benzoxaborole compounds, however, showed instability, and only 2.12b was used for in vitro biological assay and showed activity comparable to CQ. Furthermore, in vitro biological assay revealed that compounds 2.11a-g poorly inhibited the growth of P. falciparum parasites. Interestingly, these compounds, however, exhibited satisfactory activity against Trypanosoma brucei with IC50 = 0.052 μM for compound 2.11g. The cell cytotoxicity assay of all final compounds confirmed that all CQ-benzoxaborole 2.12b and cinnamoyl-benzoxaborole 2.11a-g hybrids were non-toxic against HeLa cell lines. However, efforts to further expand the structure-activity relationship (SAR) of CQbenzoxaborole by increasing the length of the linker with one extra carbon (Scheme 2.10) were not possible as an important precursor 6-formylbenzoxaborole 2.29 could not be synthesized in sufficient yields. , Thesis (MSc) -- Faculty of Faculty of Science, Chemistry, 2017
- Full Text:
- Authors: Gumbo, Maureen
- Date: 2017
- Subjects: Malaria Chemotherapy , Antimalarials , Boron compounds , Drug resistance , Plasmodium falciparum , Drug development
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/59193 , vital:27456
- Description: Malaria is a mosquito-borne disease, which continues to pose a threat to the entire humanity. About 40% of the world population is estimated to be at risk of infections by malaria. Despite efforts undertaken by scientific community, government entities and international organizations, malaria is still rampant. The major problem is drug resistance, where the Plasmodium spp have over the past decades developed drug resistance against available drugs. In order to counter this problem, novel antimalarial drugs that are efficacious and with novel mode of action are of great necessity. Benzoxaborole derivatives have been shown to exhibit promising antimalarial activity against Plasmodium falciparum strains. Previous studies reported on the compounds such as 6-(2- (alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles, which showed good antimalarial activity against both W7 and 3D7 strains without significant toxicity. On the other hand, chloroquine (CQ) and cinnamic acids have a wide variety of biological activity including antimalarial activity. Herein, a hybridisation strategy was employed to synthesise new CQ-benzoxaborole and cinnamoyl-benzoxaborole hybrids. CQ-Benzoxaborole 2.12a-c and cinnamoylbenzoxaborole 2.11a-g hydrid molecules were synthesised in low to good yields. Their structural identities were confirmed using conventional spectroscopic techniques (1H and 13C NMR, and mass spectrometry). CQ-benzoxaborole compounds, however, showed instability, and only 2.12b was used for in vitro biological assay and showed activity comparable to CQ. Furthermore, in vitro biological assay revealed that compounds 2.11a-g poorly inhibited the growth of P. falciparum parasites. Interestingly, these compounds, however, exhibited satisfactory activity against Trypanosoma brucei with IC50 = 0.052 μM for compound 2.11g. The cell cytotoxicity assay of all final compounds confirmed that all CQ-benzoxaborole 2.12b and cinnamoyl-benzoxaborole 2.11a-g hybrids were non-toxic against HeLa cell lines. However, efforts to further expand the structure-activity relationship (SAR) of CQbenzoxaborole by increasing the length of the linker with one extra carbon (Scheme 2.10) were not possible as an important precursor 6-formylbenzoxaborole 2.29 could not be synthesized in sufficient yields. , Thesis (MSc) -- Faculty of Faculty of Science, Chemistry, 2017
- Full Text:
Synthesis, characterisation and evaluation of ferrocene-containing Novobiocin analogues for anticancer and antiplasmodial activity through inhibition of Hsp90
- Authors: Mbaba, Mziyanda
- Date: 2017
- Subjects: Antibiotics Synthesis , Ferrocene , Heat shock proteins , Antimalarials , Cancer Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65111 , vital:28690
- Description: Novobiocin (Nb) is a coumarin type antibiotic isolated from the bacterium species of Streptomyces and possesses modest anticancer and antimalarial activities. Nb and analogues have been extensively explored as potential anticancer agents through inhibition of the C- terminal domain of heat shock protein 90 (Hsp90), which plays a pivotal role in the proteinfolding machinery of cells. There has been little effort in the exploration of Nb and derivatives for antimalarial activity. Incorporation of organometallic units, such as ferrocene (Fc), into bioactive chemical scaffolds remains an attractive approach for developing new therapeutic agents for treatment of several ailments. The current study sought to investigate the anticancer and antiplasmodial effects of incorporating ferrocene (Fc) into Nb scaffold presumably through inhibition of Hsp90. The ferrocenyl Nb analogues containing simplified structural motifs such as phenyl, benzyl, and piperidine were synthesized in six to nine steps employing conventional synthetic organic protocols adapted from literature, and the compounds were accessed in reasonable yields. For comparison purposes, a selection of organic Nb analogues were also included in the study. The target compounds were characterized by spectroscopic techniques including 1-dimensional nuclear magnetic resonance (1D NMR) and high-resolution mass spectroscopy. The synthesized compounds were evaluated in vitro for potential anticancer and antiplasmodial activities using the breast cancer cell line (HCC38) and chloroquine-sensitive strain (3D7) of the malaria parasite, Plasmodium falciparum. The presence of the Fc unit was found to enhance both anticancer and antiplasmodial activities of the resultant ferrocenyl Nb compounds with IC50 values in the low to mid micromolar range. Hsp90 inhibitory studies of the ferrocenyl Nb analogues possessing superior activities (2.13a and 2.20c) were also conducted using different yeast strains expressing both human and malarial Hsp90 isoforms: hHsp90a/p and PfHsp90, respectively. The results of Hsp90 inhibitory studies suggested no direct correlation between the observed activities of the analogues and Hsp90 inhibition. However, since the conditions of the assay were not optimised due to time constrains of the project, these observed data remained to be confirmed. , Thesis (MSc) -- Faculty of Science, Chemistry, 2017
- Full Text:
- Authors: Mbaba, Mziyanda
- Date: 2017
- Subjects: Antibiotics Synthesis , Ferrocene , Heat shock proteins , Antimalarials , Cancer Chemotherapy
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65111 , vital:28690
- Description: Novobiocin (Nb) is a coumarin type antibiotic isolated from the bacterium species of Streptomyces and possesses modest anticancer and antimalarial activities. Nb and analogues have been extensively explored as potential anticancer agents through inhibition of the C- terminal domain of heat shock protein 90 (Hsp90), which plays a pivotal role in the proteinfolding machinery of cells. There has been little effort in the exploration of Nb and derivatives for antimalarial activity. Incorporation of organometallic units, such as ferrocene (Fc), into bioactive chemical scaffolds remains an attractive approach for developing new therapeutic agents for treatment of several ailments. The current study sought to investigate the anticancer and antiplasmodial effects of incorporating ferrocene (Fc) into Nb scaffold presumably through inhibition of Hsp90. The ferrocenyl Nb analogues containing simplified structural motifs such as phenyl, benzyl, and piperidine were synthesized in six to nine steps employing conventional synthetic organic protocols adapted from literature, and the compounds were accessed in reasonable yields. For comparison purposes, a selection of organic Nb analogues were also included in the study. The target compounds were characterized by spectroscopic techniques including 1-dimensional nuclear magnetic resonance (1D NMR) and high-resolution mass spectroscopy. The synthesized compounds were evaluated in vitro for potential anticancer and antiplasmodial activities using the breast cancer cell line (HCC38) and chloroquine-sensitive strain (3D7) of the malaria parasite, Plasmodium falciparum. The presence of the Fc unit was found to enhance both anticancer and antiplasmodial activities of the resultant ferrocenyl Nb compounds with IC50 values in the low to mid micromolar range. Hsp90 inhibitory studies of the ferrocenyl Nb analogues possessing superior activities (2.13a and 2.20c) were also conducted using different yeast strains expressing both human and malarial Hsp90 isoforms: hHsp90a/p and PfHsp90, respectively. The results of Hsp90 inhibitory studies suggested no direct correlation between the observed activities of the analogues and Hsp90 inhibition. However, since the conditions of the assay were not optimised due to time constrains of the project, these observed data remained to be confirmed. , Thesis (MSc) -- Faculty of Science, Chemistry, 2017
- Full Text:
Synthesis, characterisation and evaluation of novel ferrocene-thiazole derivatives as antiplasmodial agents
- Authors: Hakizimana, Emmanuel Victor
- Date: 2017
- Subjects: Plasmodium , Malaria -- Chemotherapy , Plasmodium falciparum , Plasmodium -- Inhibitors , Drug resistance in microorganisms , Thiaszoles
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/5304 , vital:20807
- Description: Malaria is mosquito-transmitted disease which continues to pose threat to humanity, despite the efforts undertaken by the scientific community, government entities and international organizations. The major problem is that Plasmodium species have developed resistance against available drugs. In order to counter this problem, antimalarial drugs that are efficacious and with novel mode of action are of great necessity. Thiazole derivatives, in particular aminomethylthiazole analogues, have been shown to exhibit promising antimalarial activity against Plasmodium falciparum strains. Previous studies reported the hit compound MMV010539, which showed good antimalarial activity against both K1 (CQ and multidrug resistant strains) and NF54 (CQ sensitive strain). In this study, MMV010539 was deemed to be as an attractive compound to generate novel analogues by addition of ferrocenyl organometallic unit. The ferrocene based compounds have shown biological activity; and with ferroquine currently in clinical trials there has been increasing research into identifying new ferrocenyl-containing molecules as potential antimalarial agents. Herein, thiazole ferrocene based molecules 3.22a-e were synthesised in low to good yields. Their structural identities were confirmed using conventional spectroscopic techniques (¹H and ¹³C NMR, FT-IR spectroscopy and mass spectrometry). The cell cytotoxicity assay of all final compounds confirmed that all ferrocene-thiazole blends 3.22a-e were non-toxic against HeLa cell lines. However, the in vitro biological assay revealed that despite the absence of cell cytotoxicity these compounds poorly inhibited the growth of Plasmodium falciparum parasite. As the aim was to expand further the structure-activity relationship (SAR) of MMV010539, this study confirmed the previous findings that there is a limited structural modification that could be accommodated as indicated in Figure 3.3 (Panel C). Moreover, the combination of ferrocenyl moiety and various alkylamines resulted in compounds with poor antiplasmodial potency, further suggesting that the free amine (Panel A, Figure 3.3) is important for activity.
- Full Text:
- Authors: Hakizimana, Emmanuel Victor
- Date: 2017
- Subjects: Plasmodium , Malaria -- Chemotherapy , Plasmodium falciparum , Plasmodium -- Inhibitors , Drug resistance in microorganisms , Thiaszoles
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/5304 , vital:20807
- Description: Malaria is mosquito-transmitted disease which continues to pose threat to humanity, despite the efforts undertaken by the scientific community, government entities and international organizations. The major problem is that Plasmodium species have developed resistance against available drugs. In order to counter this problem, antimalarial drugs that are efficacious and with novel mode of action are of great necessity. Thiazole derivatives, in particular aminomethylthiazole analogues, have been shown to exhibit promising antimalarial activity against Plasmodium falciparum strains. Previous studies reported the hit compound MMV010539, which showed good antimalarial activity against both K1 (CQ and multidrug resistant strains) and NF54 (CQ sensitive strain). In this study, MMV010539 was deemed to be as an attractive compound to generate novel analogues by addition of ferrocenyl organometallic unit. The ferrocene based compounds have shown biological activity; and with ferroquine currently in clinical trials there has been increasing research into identifying new ferrocenyl-containing molecules as potential antimalarial agents. Herein, thiazole ferrocene based molecules 3.22a-e were synthesised in low to good yields. Their structural identities were confirmed using conventional spectroscopic techniques (¹H and ¹³C NMR, FT-IR spectroscopy and mass spectrometry). The cell cytotoxicity assay of all final compounds confirmed that all ferrocene-thiazole blends 3.22a-e were non-toxic against HeLa cell lines. However, the in vitro biological assay revealed that despite the absence of cell cytotoxicity these compounds poorly inhibited the growth of Plasmodium falciparum parasite. As the aim was to expand further the structure-activity relationship (SAR) of MMV010539, this study confirmed the previous findings that there is a limited structural modification that could be accommodated as indicated in Figure 3.3 (Panel C). Moreover, the combination of ferrocenyl moiety and various alkylamines resulted in compounds with poor antiplasmodial potency, further suggesting that the free amine (Panel A, Figure 3.3) is important for activity.
- Full Text: