CO2-induced woody thickening depends strongly on interacting abiotic and biotic factors
- Authors: Raubenheimer, Sarah Lynn
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164646 , vital:41151 , doi:10.21504/10962/164646
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Botany, 2020
- Full Text:
- Date Issued: 2020
- Authors: Raubenheimer, Sarah Lynn
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164646 , vital:41151 , doi:10.21504/10962/164646
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Botany, 2020
- Full Text:
- Date Issued: 2020
Comparative analysis of the known Hop1b and the novel Hop1a isoforms of the Hop gene
- Authors: Makhubu, Portia
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164311 , vital:41108 , doi:10.21504/10962/164311
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Makhubu, Portia
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164311 , vital:41108 , doi:10.21504/10962/164311
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Design of Immunobiosensors for Detection of Tumor-Associated Anti-P53 Autoantibodies: Method Development
- Authors: Adeniyi, Omotayo Kayode
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/162988 , vital:41002 , 10.21504/10962/162988
- Description: Introduction -- Experimental -- Label-Free Impedimetric Sensing of Anti-P53ab... -- Fluorescent detection of Anti-P53ab -- Peroxidase-like activity of Fe3O4@SiNP-APTES-Au@Pd... -- Colorimetric detection of Anti-P53ab , Thesis (PhD)--Rhodes University, Science Faculty, Department of Chemistry, 2020. , Detection and profiling of circulating tumor-associated autoantibodies (TAAbs) are useful for screening and early-stage diagnosis of asymptomatic lung cancer. Immunobiosensor technologies aimed to accomplish the highly sensitive, rapid and low-cost detection of TAAbs can improve the early-stage detection of lung cancer. Immunobiosensors for the detection of anti-P53-tumour associated autoantibodies have been developed in this work. The design of sensing interfaces with immobilized P53 protein (P53ag) as a sensing element layer on a solid interface was investigated. Several methods of detecting anti-P53-antibodies (anti-P53ab) were investigated. These methods are label-free detection using electrochemical impedance spectroscopy (EIS) and two label techniques. The label-free electrochemical techniques utilize gold electrode pre-modified with a conducting layer of electrochemically grafted phenylethylamine for covalent immobilization of P53ag. The limit of anti-P53ab detection with the label-free EIS was 103.0 pg.ml-1. The labeled technique developed utilizes fluorescent, and peroxidase-like nanomaterial labeled antibody as a detection probe. For the fluorescence detection, fluorescent silica nanoparticles were synthesized by overloading FITC into the silica matrix and conjugated to detection antibody (anti-IgG). The detection of the anti-P53ab was based on the dissolution of the silica nanoparticles to release the loaded dye as a signal amplification strategy. The fluorescence detection was carried out on a microplate, and magnetic bead modified P53-antigen platforms and limit of detection (LoD) were 42.0 fg.ml-1 and 3.3 fg.ml-1 for anti-P53ab; respectively. Fe3O4@SiNP-APTES-Au@Pd hybrid nanoparticles were synthesized, and their peroxidase-like activity and colorimetric detection were evaluated. The Fe3O4@SiNP-APTES-Au@Pd exhibited comparable activity to HRP. The Fe3O4@SiNP-APTES-Au@Pd was conjugated to protein-G-anti-IgG for the detection of anti-P53ab on a microplate and cellulose paper platforms. The LoD was 20.0 fg.ml-1 and 63.0 fg.ml-1 for the microplate and cellulose paper platform; respectively. The potential application of the designed immunobiosensor was evaluated in simulated serum samples. The developed sensors showed higher detection sensitivity, stability and had a lower detection limit for anti-P53ab when compared with the ELISA based detection. The results have provided alternative and effective quantification approaches to ELISA and a promising future for multiplexed detection of tumor-associated autoantibodies. The developed methodologies in this thesis could be applied for the detection of other autoantibodies in other cancer types and auto-immune diseases.
- Full Text:
- Date Issued: 2020
- Authors: Adeniyi, Omotayo Kayode
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/162988 , vital:41002 , 10.21504/10962/162988
- Description: Introduction -- Experimental -- Label-Free Impedimetric Sensing of Anti-P53ab... -- Fluorescent detection of Anti-P53ab -- Peroxidase-like activity of Fe3O4@SiNP-APTES-Au@Pd... -- Colorimetric detection of Anti-P53ab , Thesis (PhD)--Rhodes University, Science Faculty, Department of Chemistry, 2020. , Detection and profiling of circulating tumor-associated autoantibodies (TAAbs) are useful for screening and early-stage diagnosis of asymptomatic lung cancer. Immunobiosensor technologies aimed to accomplish the highly sensitive, rapid and low-cost detection of TAAbs can improve the early-stage detection of lung cancer. Immunobiosensors for the detection of anti-P53-tumour associated autoantibodies have been developed in this work. The design of sensing interfaces with immobilized P53 protein (P53ag) as a sensing element layer on a solid interface was investigated. Several methods of detecting anti-P53-antibodies (anti-P53ab) were investigated. These methods are label-free detection using electrochemical impedance spectroscopy (EIS) and two label techniques. The label-free electrochemical techniques utilize gold electrode pre-modified with a conducting layer of electrochemically grafted phenylethylamine for covalent immobilization of P53ag. The limit of anti-P53ab detection with the label-free EIS was 103.0 pg.ml-1. The labeled technique developed utilizes fluorescent, and peroxidase-like nanomaterial labeled antibody as a detection probe. For the fluorescence detection, fluorescent silica nanoparticles were synthesized by overloading FITC into the silica matrix and conjugated to detection antibody (anti-IgG). The detection of the anti-P53ab was based on the dissolution of the silica nanoparticles to release the loaded dye as a signal amplification strategy. The fluorescence detection was carried out on a microplate, and magnetic bead modified P53-antigen platforms and limit of detection (LoD) were 42.0 fg.ml-1 and 3.3 fg.ml-1 for anti-P53ab; respectively. Fe3O4@SiNP-APTES-Au@Pd hybrid nanoparticles were synthesized, and their peroxidase-like activity and colorimetric detection were evaluated. The Fe3O4@SiNP-APTES-Au@Pd exhibited comparable activity to HRP. The Fe3O4@SiNP-APTES-Au@Pd was conjugated to protein-G-anti-IgG for the detection of anti-P53ab on a microplate and cellulose paper platforms. The LoD was 20.0 fg.ml-1 and 63.0 fg.ml-1 for the microplate and cellulose paper platform; respectively. The potential application of the designed immunobiosensor was evaluated in simulated serum samples. The developed sensors showed higher detection sensitivity, stability and had a lower detection limit for anti-P53ab when compared with the ELISA based detection. The results have provided alternative and effective quantification approaches to ELISA and a promising future for multiplexed detection of tumor-associated autoantibodies. The developed methodologies in this thesis could be applied for the detection of other autoantibodies in other cancer types and auto-immune diseases.
- Full Text:
- Date Issued: 2020
Design of immunosensor for the detection of C-reactive protein using oriented antibody immobilization
- Authors: Adesina, Abiola Olanike
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163080 , vital:41010 , https://dx.doi.org/10.21504/10962/163080
- Description: Thesis (PhD)--Rhodes University, Science Faculty, Department of Chemistry, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Adesina, Abiola Olanike
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163080 , vital:41010 , https://dx.doi.org/10.21504/10962/163080
- Description: Thesis (PhD)--Rhodes University, Science Faculty, Department of Chemistry, 2020.
- Full Text:
- Date Issued: 2020
Development and assessment of a fixed dose combination of perindopril arginine and indapamide loaded microparticles
- Authors: Mandava, Tavonga Tyomai
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164413 , vital:41116
- Description: Thesis (MSc)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
- Authors: Mandava, Tavonga Tyomai
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164413 , vital:41116
- Description: Thesis (MSc)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
Development of a low-cost bioprinting system for engineering of Human Tumour Models
- Authors: Fanucci, Sidne
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163295 , vital:41026
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Fanucci, Sidne
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163295 , vital:41026
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020.
- Full Text:
- Date Issued: 2020
Development of a protocol for extracting and quantifying the concentration of thiafentanil in blesbok (Damaliscus pygargus phillipsi) matrices 72-74 hours post administration
- Authors: Webber, Judith Tracy
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164738 , vital:41159
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
- Authors: Webber, Judith Tracy
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164738 , vital:41159
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
Development of paper-based aptasensors for detection of Plasmodium falciparum lactate dehydrogenase in malaria
- Ogunmolasuyi, Adewoyin Martin
- Authors: Ogunmolasuyi, Adewoyin Martin
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164601 , vital:41147 , doi:10.21504/10962/164601
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020
- Full Text:
- Date Issued: 2020
- Authors: Ogunmolasuyi, Adewoyin Martin
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164601 , vital:41147 , doi:10.21504/10962/164601
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020
- Full Text:
- Date Issued: 2020
Formulation and characterisation of a combination captopril and hydrochlorothiazide microparticulate dosage form for paediatric use
- Chikukwa, Mellisa Tafadzwa Ruramai
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163216 , vital:41019 , doi:10.21504/10962/163216
- Description: Thesis (PhD)--Rhodes University, Pharmacy Faculty, Department of Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
- Authors: Chikukwa, Mellisa Tafadzwa Ruramai
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/163216 , vital:41019 , doi:10.21504/10962/163216
- Description: Thesis (PhD)--Rhodes University, Pharmacy Faculty, Department of Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
Formulation, development and assessment of devil’s claw loaded phyto-elastosomes in thermo-responsive hydrogels
- Authors: Ntemi, Pascal Vitalis
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164568 , vital:41139 , doi:10.21504/10962/164568
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
- Authors: Ntemi, Pascal Vitalis
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164568 , vital:41139 , doi:10.21504/10962/164568
- Description: Thesis (PhD)--Rhodes University, Faculty of Pharmacy, Pharmaceutics, 2020
- Full Text:
- Date Issued: 2020
Hop as an anti-cancer drug target
- Vaaltyn, Michaelone Chantelle
- Authors: Vaaltyn, Michaelone Chantelle
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164704 , vital:41156 , doi:10.21504/10962/164704
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Vaaltyn, Michaelone Chantelle
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164704 , vital:41156 , doi:10.21504/10962/164704
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Investigating cell culture models for improved understanding of adipose tissue and co-morbidities in vitro
- Authors: Stoffels, Mihlali
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164674 , vital:41154
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020
- Full Text:
- Date Issued: 2020
- Authors: Stoffels, Mihlali
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164674 , vital:41154
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biotechnology Innovation Centre, 2020
- Full Text:
- Date Issued: 2020
Investigating the relationship between Heat Shock Proteins and HIV Transactivator of Transcription
- Authors: Flax, Lili Marie
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163307 , vital:41027
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Flax, Lili Marie
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/163307 , vital:41027
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020.
- Full Text:
- Date Issued: 2020
Livelihood implications of a possible Ramsar declaration of the Swartkops estuary, Eastern Cape, South Africa
- Authors: Vembo, Glen Muchengeti
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164715 , vital:41157
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Environmental Science, 2020
- Full Text:
- Date Issued: 2020
- Authors: Vembo, Glen Muchengeti
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164715 , vital:41157
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Environmental Science, 2020
- Full Text:
- Date Issued: 2020
Molecular and morphological approaches reveal hidden diversity in the genus hippopotamyrus pappenheim, 1906 (teleostei: mormyridae) in southern Africa
- Authors: Mutizwa, Tadiwa, Isaac
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164546 , vital:41128
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Department of Icthyology and Fisheries Science, 2020
- Full Text:
- Date Issued: 2020
- Authors: Mutizwa, Tadiwa, Isaac
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164546 , vital:41128
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Department of Icthyology and Fisheries Science, 2020
- Full Text:
- Date Issued: 2020
Multiplexed Mass Spectrometry: Single, On-Bead, Detection Analysis Using MALDI-TOF MS
- Authors: Twala, Busisiwe Victoria
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164693 , vital:41155 , doi:10.21504/10962/164693
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Twala, Busisiwe Victoria
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164693 , vital:41155 , doi:10.21504/10962/164693
- Description: Thesis (PhD)--Rhodes University, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Nutrient impacts on grasses and legumes growing in communal pasture soil in relation to mycorrhizal activity
- Authors: Mkile, Zolani
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164512 , vital:41125 , doi:10.21504/10962/164512
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Mkile, Zolani
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Doctoral , PhD
- Identifier: http://hdl.handle.net/10962/164512 , vital:41125 , doi:10.21504/10962/164512
- Description: Thesis (PhD)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Orchid mycorrhizal and endophytic fungal diversity of three cooccurring terrestrial orchids in the large African genus Disa (Orchidaceae)
- Authors: Le Du, Bridgitte M
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MA
- Identifier: http://hdl.handle.net/10962/163363 , vital:41033
- Description: Thesis (MA)--Rhodes University, Faculty of Humanities, English Language and Linguistics, 2020.
- Full Text:
- Date Issued: 2020
- Authors: Le Du, Bridgitte M
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MA
- Identifier: http://hdl.handle.net/10962/163363 , vital:41033
- Description: Thesis (MA)--Rhodes University, Faculty of Humanities, English Language and Linguistics, 2020.
- Full Text:
- Date Issued: 2020
Production, purification and characterization of a multifunctional, thermostable and acido/alkaline stable putative xylanase from the psychrotrophic bacterium, Sphingomonas aerolata
- Authors: Mathibe, Brian Nkanyiso
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164478 , vital:41122
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
- Authors: Mathibe, Brian Nkanyiso
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: thesis , text , Masters , MSc
- Identifier: http://hdl.handle.net/10962/164478 , vital:41122
- Description: Thesis (MSc)--Rhodes University, Faculty of Science, Biochemistry and Microbiology, 2020
- Full Text:
- Date Issued: 2020
Repurposing a polymer precursor scaffold for medicinal application: Synthesis, characterization and biological evaluation of ferrocenyl 1,3-benzoxazine derivatives as potential antiprotozoal and anticancer agents
- Authors: Mbaba, Mziyanda
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164502 , vital:41124 , DOI 10.21504/10962/164502
- Description: The benzoxazines are a prominent class of heterocyclic compounds that possess a multitude of properties. To this end, benzoxazine derivatives have been used as versatile compounds for various utilities ranging from biological applications to the fabrication of polymers. Particularly, the 1,3-benzoxazine scaffold has featured in several bioactive compounds showing antimalarial, anticancer and antibacterial activities. Traditionally, it has been employed as a substrate in the synthesis of polymers with appealing physical and chemical properties. Due to the increasing interest in the polymer application of 1,3-benzoxazines, research of the 1,3-benzoxazine motif for polymer synthesis has been prioritized over other applications including its medicinal potential. The continuous development of resistance to clinical anticancer and antimalarial drugs has necessitated the need for the search of innovative bioactive compounds as potential alternative medicinal agents. To address this, the field of medicinal chemistry is adapting new approaches to counter resistance by incorporating nonconventional chemical moieties such as organometallic complexes, like ferrocene, into bioactive chemical motifs to serve as novel compounds with medicinal benefits. Incorporation of ferrocene into known bioactive chemical moieties has been shown to impart beneficial biological effects into the resultant compounds, which include the introduction of novel, and sometimes varied, mechanistic modalities and enhanced potency. Presented with the benefits of this strategy, the current work aims to design and evaluate the pharmaceutical capacity of novel derivatives containing 1,3-benzoxazine scaffold (traditionally applied in polymer synthesis) hybridized with the organometallic ferrocene unit as bioactive agents. Using a combination of expedient synthetic procedures such as the Burke three-component Mannich-type condensation, Vilsmeier-Haack formylation and reductive amination, four series of ferrocenyl 1,3-benzoxazine derivatives were synthesized and their structures confirmed by common spectroscopic techniques: nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). The target compounds were evaluated in vitro for potential antimalarial and anticancer activities against strains of the malaria parasite (Plasmodium falciparum 3D7 and Dd2) and the triple-negative breast cancer cell line HCC70. Compounds exhibited higher potency towards the Plasmodium falciparum strains with IC50 values in the low and sub-micromolar range in comparison to the breast cancer cell line against for which mid-molar activities were observed. To gain insight into the possible mode of action of ferrocenyl 1,3-benzoxazines, representative compounds showing most efficacy from each series were assessed for DNA binding affinity by employing UV-Vis and fluorescence DNA titration experiments. The selected compounds were found to interact with the DNA by binding to the minor groove, and these findings were confirmed by in silico ligand docking studies using a B-DNA structure as the receptor. Compound 3.16c (IC50: 0.261 μM [3D7], 0.599 μM [Dd2], 11.0 μM [HCC70]), which emerged as the most promising compound, was found to induce DNA damage in HCC70 cancer cells when investigated for effects of DNA interaction. Additionally, compound 3.16c displayed a higher binding constant (Kb) against DNA isolated from 3D7 Plasmodium falciparum trophozoites (Kb = 1.88×106 M-1) than the mammalian DNA (Kb = 6.33×104 M-1) from calf thymus, thus explaining the preferred selectivity of the compounds for the malaria parasite. Moreover, the investigated compounds demonstrated binding affinity for synthetic hemozoin, β-hematin. Collectively, these data suggest that the compounds possess a dual mode of action for antimalarial activity involving DNA interaction and hemozoin inhibition. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020
- Authors: Mbaba, Mziyanda
- Date: 2020
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164502 , vital:41124 , DOI 10.21504/10962/164502
- Description: The benzoxazines are a prominent class of heterocyclic compounds that possess a multitude of properties. To this end, benzoxazine derivatives have been used as versatile compounds for various utilities ranging from biological applications to the fabrication of polymers. Particularly, the 1,3-benzoxazine scaffold has featured in several bioactive compounds showing antimalarial, anticancer and antibacterial activities. Traditionally, it has been employed as a substrate in the synthesis of polymers with appealing physical and chemical properties. Due to the increasing interest in the polymer application of 1,3-benzoxazines, research of the 1,3-benzoxazine motif for polymer synthesis has been prioritized over other applications including its medicinal potential. The continuous development of resistance to clinical anticancer and antimalarial drugs has necessitated the need for the search of innovative bioactive compounds as potential alternative medicinal agents. To address this, the field of medicinal chemistry is adapting new approaches to counter resistance by incorporating nonconventional chemical moieties such as organometallic complexes, like ferrocene, into bioactive chemical motifs to serve as novel compounds with medicinal benefits. Incorporation of ferrocene into known bioactive chemical moieties has been shown to impart beneficial biological effects into the resultant compounds, which include the introduction of novel, and sometimes varied, mechanistic modalities and enhanced potency. Presented with the benefits of this strategy, the current work aims to design and evaluate the pharmaceutical capacity of novel derivatives containing 1,3-benzoxazine scaffold (traditionally applied in polymer synthesis) hybridized with the organometallic ferrocene unit as bioactive agents. Using a combination of expedient synthetic procedures such as the Burke three-component Mannich-type condensation, Vilsmeier-Haack formylation and reductive amination, four series of ferrocenyl 1,3-benzoxazine derivatives were synthesized and their structures confirmed by common spectroscopic techniques: nuclear magnetic resonance (NMR), infrared spectroscopy (IR) and high-resolution mass spectrometry (HRMS). The target compounds were evaluated in vitro for potential antimalarial and anticancer activities against strains of the malaria parasite (Plasmodium falciparum 3D7 and Dd2) and the triple-negative breast cancer cell line HCC70. Compounds exhibited higher potency towards the Plasmodium falciparum strains with IC50 values in the low and sub-micromolar range in comparison to the breast cancer cell line against for which mid-molar activities were observed. To gain insight into the possible mode of action of ferrocenyl 1,3-benzoxazines, representative compounds showing most efficacy from each series were assessed for DNA binding affinity by employing UV-Vis and fluorescence DNA titration experiments. The selected compounds were found to interact with the DNA by binding to the minor groove, and these findings were confirmed by in silico ligand docking studies using a B-DNA structure as the receptor. Compound 3.16c (IC50: 0.261 μM [3D7], 0.599 μM [Dd2], 11.0 μM [HCC70]), which emerged as the most promising compound, was found to induce DNA damage in HCC70 cancer cells when investigated for effects of DNA interaction. Additionally, compound 3.16c displayed a higher binding constant (Kb) against DNA isolated from 3D7 Plasmodium falciparum trophozoites (Kb = 1.88×106 M-1) than the mammalian DNA (Kb = 6.33×104 M-1) from calf thymus, thus explaining the preferred selectivity of the compounds for the malaria parasite. Moreover, the investigated compounds demonstrated binding affinity for synthetic hemozoin, β-hematin. Collectively, these data suggest that the compounds possess a dual mode of action for antimalarial activity involving DNA interaction and hemozoin inhibition. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2020