Browsing by Author "Madiehe, Abram M."

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    Bis(ferrocenylimine)palladium(II) and platinum(II) complexes: synthesis, molecular structures and evaluation as antitumor agents
    (Elsevier, 2012) Motswainyana, William M.; Onani, Martin O.; Madiehe, Abram M.
    Compounds (ferrocenyl-2-furylmethyl)imine (L1), (ferrocenyl-2-thiophenemethyl)imine (L2) and (ferrocenyl-2-thiopheneethyl)imine (L3) were synthesized by condensation reactions and obtained in very good yields. Reactions of L1 – L3 with 0.5 equiv of either PdCl2(cod), PdClMe(cod) or K2[PtCl4] gave the new corresponding trans bis(ferrocenylimine)palladium(II) and platinum(II) complexes 1 – 9. The compounds were characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy. The molecular structures of 3 and 6 were determined by single crystal X-ray diffraction analysis. Both structures crystallize in monoclinic P21/n space system. The coordination geometry around the palladium atom in complexes 3 and 6 exhibits a square planar geometry at the palladium atom. Complexes 1, 7 and 9 were evaluated for their cytotoxic activities against human breast (MCF-7) and human ovarian (A2780) cancer cell lines, and they exhibited low cytotoxic activities but comparable to that of cisplatin.
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    Development of a receptor targeted nanotherapy using a proapoptotic peptide
    (University of the Western Cape, 2015) Sibuyi, Nicole Remaliah Samantha; Meyer, Mervin; Madiehe, Abram M.
    The prevalence of obesity amongst South Africans is alarming, with more than 29% of men and 56% of women considered to be obese. Angiogenesis, a process for development of new blood vessels play a major role in growth and survival of the adipose tissues. Pharmacological inhibitors of angiogenesis are therefore a sensible strategy to reduce excess body weight. Current anti-obesity drugs have limitations because of their lack of selectivity and specificity, which lead to undesirable side effects and reduced drug efficacy. Future anti-obesity therapeutic strategies should be target-specific, with minimal toxicity towards healthy tissues will be more appropriate for obesity treatment. Targeted nano-therapeutic agents are currently being developed to overcome the drawbacks associated with conventional drug therapies. The nano-based delivery vehicles that specifically target diseased cells are appealing as they could reduce drug toxicity towards healthy tissues and be more effective at lower dosages. The main aim of this study was to develop a receptor-mediated nanotherapy that specifically targets the white adipose tissue vasculature and trigger the death of these cells through apoptosis. The 14 nm gold nanoparticles (AuNPs) were synthesized using theTurkevich method following reduction of gold aurate by sodium citrate salt. Different chemistries were used to functionalise the AuNPs for biological application by conjugating with either vascular targeting peptide or pro-apoptotic peptide on their surface or both. The nanomaterials were characterised by UV-Vis, Zeta potential and transmission electron microscopy (TEM). The sensitivity and specificity of various AuNP conjugates were tested in vitro on colon and breast cancer cell lines. A human (Caco-2) cell line that expresses the receptor for the adipose homing peptide was chosen as an in vitro model system. Cellular toxicity and uptake of the nanoparticles was evaluated using the WST-1 assay, Inductively Coupled Plasma-Optical Emission Spectra (ICP-OES) and TEM. The induction of apoptosis following exposure to the nanoparticles was examined by Western blot and flow cytometric analysis. The anti-proliferative activity of the targeted therapeutic nanoparticles on the cells was more pronounced on the cells expressing the receptor for the adipose homing peptide. The uptake of unfunctionalised AuNPs was higher compared to functionalised nanoparticles, but this did not impair cell viability. The activity of the therapeutic peptide was retained and enhanced following conjugation to AuNPs as shown by Western blot and flow cytometric analysis. The nanotherapy under study demonstrated receptor mediated targeting, and enhanced activity on the cells expressing the receptor. However, the therapeutic and efficacy of the targeted nanotherapy still need to be tested in animal models of obesity to confirm the treatment specificity.
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    Development of nanotechnology-based drug delivery and imaging system to the white adipose tissue vasculature using Wistar Rat Model
    (University of the Western Cape, 2013) Thovhogi, Ntevheleni; Madiehe, Abram M.; Meyer, Mervin M.
    Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people and its pharmacological management is hampered by drug toxicity and undesirable side effects. Therefore, a need still exists for the development of safe medication for treatment of obesity. Nanotechnology involves the use of small particles at atomic and molecular scale. It has application in medical diagnostics, drug delivery and molecular imaging. Various nanoparticles (NPs) functionalized with different biomolecules have been successfully used in many therapeutic and research applications due to their versatility, ease of chemical synthesis, low toxicity and unique properties. Examples of NPs used in this study are Gold nanoparticles (GNPs) and Quantum dots (QDs). GNPs and QDs are extensively used as drug delivery, labelling and imaging tools in biomedical research. Nanotechnology offers a new potential useful avenue for solving the problem of toxicity of anti-obesity drugs. This could be achieved through targeted drug delivery. In this study, rats were fed a high fed diet (HFD) to induce obesity. The streptavidin conjugated GNPs and QDs were functionalized with biotinylated adipose-homingpeptide (AHP) and/or anti-obesity drug (Gallic acid). Functionalization was characterized using agarose gel electrophoresis, UV-vis spectroscopy and transmission electron microscopy. The binding-specificity and targeting ability of AHP was evaluated in vitro and in vivo. The apoptotic effect of AHP functionalized-drug loaded GNPs (AHP-GA-GNPs) was tested in vitro using APOPercentage TM and Caspase-3 activation assays. The in vitro data indicated that the binding was specific to prohibitin (PHB) expressing cells (MCF-7 and Caco-2), and that the binding was temperature dependent. PHB was confirmed as a target for AHP after overlaying AHP-FITC and anti-prohibitin antibody staining. Cellular uptake was detected on the cells treated with AHP-functionalized NPs as compared to unfunctionalized NPs. The GA and AHP-GA-GNPs reduced cellular viability and induced apoptosis through activation of Caspase-3. The Ex-vivo studies using primary endothelial cells (ECs) isolated from the WAT of lean and obese Wistar rats showed that the binding of AHP was receptor mediated, and specific to receptors differentially expressed in ECs from obese WAT. The in vivo studies showed that, treatment of obese rats with AHP-functionalized NPs resulted in targeted delivery of the NPs to the WAT as compared to those treated with unfunctionalized NPs. Qualitative analysis using fluorescence microscopy and IVIS Luminar XR, live-imaging system showed that the unfunctionalized NPs accumulated mostly in the organs of the reticuloendothelial system, namely: liver, spleen, lungs and kidneys. In contrast, AHP-functionalized NPs accumulated mostly in the WATs as compared to the rest of the organs of the obese rats. Uptake and binding of the NPs to the tissues was quantitatively confirmed by the inductive coupled plasma-optical emission spectroscopy (ICP-OES). In conclusion, this study reports the 1) successful functionalization of GNPs and QDs with AHP, 2) use of AHP-functionalized GNPs and QDs as delivery and imaging agents to the WAT, and 3) potential use of AHP-functionalized drug-loaded GNPs in the treatment of obesity.
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    Identification of differentially expressed proteins in obese rats fed different high fat diets using proteomics and bioinformatics approaches
    (2013) Gabuza, Kwazikwakhe; Ndimba, Bongani K.; Madiehe, Abram M.
    Obesity is a medical condition in which an energy imbalance leads to excessive accumulation of body fat. Obesity leads to a reduction in life expectancy through its association with chronic diseases of lifestyle. The prevalence of obesity is rapidly increasing throughout the world. It is now accepted that most cases of obesity result from an interaction between genetic and environmental factors. This rapid increase in obesity generally leads to an increase in morbidity and mortality from chronic diseases such as cardiovascular disease, type 2 diabetes, osteoarthritis and cancer of which obesity is a risk factor. There is a lack of information in molecular research to explain how obesity predisposes individuals to these diseases. Proteomics is a molecular tool and a set of techniques used to identify changes at protein level from a diseased state. This study aims to identify differentially expressed proteins in serum of obese rats fed different isocaloric diets using proteomics.
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    Imino-phospine palladium (II) and platinum (II) complexes: Synthesis, molecular structures and evaluation as antitumor agents
    (Elsevier, 2013) Motswainyana, William M.; Onani, Martin O.; Madiehe, Abram M.; Saibu, Morounke; Thovhogi, Ntevheleni; Lalancette, Roger A.
    The imino-phosphine ligands L1 and L2 were prepared via condensation reaction of 2-(diphenylphosphino) benzaldehyde with substituted anilines and obtained in very good yields. An equimolar reaction of L1 and L2 with either PdCl2(cod) or PtCl2(cod) gave new palladium(II) and platinum(II) complexes 1–4. The compounds were characterized by elemental analysis, IR, 1H and 31P NMR spectroscopy. The molecular structures of 2, 3 and 4 were confirmed by X-ray crystallography. All the three molecular structures crystallized in monoclinic C2/c space system. The coordination geometry around the palladiumand platinumatoms in respective structures exhibited distorted square planar geometry at the metal centers. The complexes were evaluated in vitro for their cytotoxic activity against human breast (MCF-7) and human colon (HT-29) cancer cells, and they exhibited growth inhibitory activities and selectivity that were superior to the standard compound cisplatin.
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    Imino-quinolyl palladium(II) and platinum(II) complexes: synthesis, characterization, molecular structures and cytotoxic effect
    (Elsevier, 2013) Motswainyana, William M.; Onani, Martin O.; Madiehe, Abram M.; Saibu, Morounke; Jacobs, Jeroen; van Meervelt, Luc
    Imino-quinolyl ligands L1-L5 were synthesized by condensation reactions and obtained in good yields. Reactions of the ligands with either PdCl2(cod) or K2[PtCl4] gave the corresponding palladium(II) and platinum(II) complexes 1-10 also in good yields. All the compounds were characterized by elemental analysis, IR, 1H and 13C NMR spectroscopy. X-ray crystallography was used to confirm the structures of these compounds. Molecular structures of 3 and 5 showed that the ligands coordinate to the metal centre through the two nitrogen atoms, generating a distorted square planar geometry around the palladium atom. The new complexes exhibited remarkable cytotoxic activities against MCF-7 and HT-29 cancer cell lines.
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    One-pot synthesis and characterization of InP/ZnSe semiconductor nanocrystals
    (Elsevier, 2013) Mushonga, Paul; Onani, Martin O.; Madiehe, Abram M.; Meyer, Mervin
    We report on the one-pot synthesis of InP/ZnSe quantum dots (QDs) using a precursor-based colloidal synthesis in a noncoordinating solvent environment. The structural and optical studies were carried out on the as-prepared InPQDs. The quantum yield of the nanocrystals was recorded as 6% and a 1.4 times reduction in the ratio of trap-related emission to band edge emission was observed on ZnSe passivation of the InPQDs.