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Durban, South Africa

Traut-Johnstone T.,University of Johannesburg | Traut-Johnstone T.,Mintek | Kanyanda S.,University of the Western Cape | Kriel F.H.,Mintek | And 12 more authors.
Journal of Inorganic Biochemistry | Year: 2015

New heteroditopic, bi- and multidentate imino- and aminophosphine ligands were synthesised and complexed to [AuCl(THT)] (THT = tetrahydrothiophene). X-ray crystallography confirmed Schiff base formation in three products, the successful reduction of the imino-group to the sp3-hybridised amine in several instances, and confirmed the formation of mono-gold(I) imino- and aminophosphine complexes for four Au-complexes. Cytotoxicity studies in cancerous and non-cancerous cell lines showed a marked increase in cytotoxicity upon ligand complexation to gold(I). These findings were supported by results from the 60-cell line fingerprint screen of the Developmental Therapeutics Programme of the National Institutes of Health for two promising compounds. The cytotoxicity of some of these ligands and gold(I)complexes is due to the induction of apoptosis. The ligands and gold(I)complexes demonstrated selective toxicity towards specific cell lines, with Jurkat T cells being more sensitive to the cytotoxic effects of these compounds, while the non-cancerous human cell line KMST6 proved more resistant when compared to the cancerous cell lines. Results from the NIH DTP 60 cell-line fingerprint screen support the observed enhancement of cytotoxicity upon gold(I) complexation. One gold(I)complex induced high levels of apoptosis at concentrations of 50 μM in all the cell lines screened in this study, while some of the other compounds selectively induced apoptosis in the cell lines. These results point towards the potential for selective toxicity to cancerous cells through the induction of apoptosis. © 2015 Elsevier Inc. All rights reserved. Source

Dlamini Z.,Mangosuthu University of Technology | Ntlabati P.,Merck And Co. | Mbita Z.,University of Limpopo | Shoba-Zikhali L.,Technology Innovation Agency
Experimental and Molecular Pathology | Year: 2015

Pyruvate dehydrogenase kinase 4 (PDK4), a mammalian mitochondrial serine kinase has emerged as an interesting candidate for diabetes therapy. Due to the high prevalence of this disease especially type 2 diabetes (T2D) and the health complications associated with it, there is extensive effort to find the appropriate treatment. Understanding the regulation of PDK4 activity would therefore contribute significantly to the development of therapeutic agents. This research outlines the utilization of bioinformatics tools such as Interweaver, ClustalW and Protein Structure Visualizer, in order to predict proteins that potentially interact with PDK4 and possibly regulate its activity. Interweaver database identified 96 proteins that have possible interaction sites for PDK4. Protein p100/p49, containing a death domain that is known to have a role in suppressing apoptosis, was identified as a potential partner for PDK4. The alignment between p100/p49 primary sequence and that of PDK4 using ClustalW demonstrated sequence similarity between the two proteins. Swiss PDB Viewer then located the positions of the amino acids that are in the hypothetical protein binding motif of p100/p49 within the 3D structure of hPDK4. These amino acids were found to be located in the region of PDK4 which is known to bind protein substrates of PDK4 and may be accessible to other proteins as well. These findings were very interesting as PDK4 has not previously been associated with apoptosis and this could be the link between apoptosis and insulin resistance. Cell biology studies were then performed to verify the relationship between PDK4 and apoptosis. In this regard, HeLa and HepG2 cells were treated with apoptosis-inducing agents such as TNFα, C2-ceramide, and linoleic acid. These cells were then monitored for apoptosis and PDK4 mRNA expression using a DNA laddering assay as well as Real Time PCR. The results showed that these factors induced apoptosis in a concentration dependent manner and suppressed PDK4 mRNA levels. These findings suggested a relationship between PDK4 and apoptosis. © 2015. Source

Fayomi O.S.I.,Covenant University | Fayomi O.S.I.,Tshwane University of Technology | Fayomi O.S.I.,Technology Innovation Agency
Journal of Materials and Environmental Science | Year: 2015

Co-deposition of zinc metal matrix with ZnO composite was fabricated from electrolytic chloride based coating consisting of 20-40g/L ZnO particle. The resulting composite coatings were characterized using high optic microscope (OPM). The corrosion resistance properties of Zn-ZnO composite coatings were measure using linear polarization in 3.5% NaCl solution. The variation of amount of ZnO %wt. inclusion of the composite on micro-hardness was investigated using dura scan diamond base micro-hardness tester. The results obtained indicate that the introduction of ZnO particles in the deposition bath obviously increase significantly the hardness properties. The increases in hardness value are attributed to the realization of coherent and even precipitate into the metal lattice. The corrosion polarization resistance also improved slightly as against the MS. It was found that addition of ZnO %wt support strengthening characteristics toward hardness improvement with slight enhancement in anti-corrosion properties. Source

Paquet T.,University of Cape Town | Gordon R.,Technology Innovation Agency | Waterson D.,ICC Inc | Witty M.J.,ICC Inc | Chibale K.,University of Cape Town
Future Medicinal Chemistry | Year: 2012

The current state of antimalarial drug resistance emphasizes the need for new therapies with novel modes of action that will add a significant benefit compared with current standards. In this regard, high throughput phenotypic whole-cell screening aids the discovery of novel antiplasmodial scaffolds that are inherently suited to hit-to-lead and lead-optimization efforts. The aminothiazoles and aminopyridines exemplify two such compound classes stemming from whole-cell screening. Respective structure-activity relationship determinations and subsequent optimization around these scaffolds led to frontrunner compounds in each series, which possess the desired antimalarial efficacy, bioavailability and metabolic stability to further progress medicinal chemistry programs. © 2012 Future Science Ltd. Source

Nwaka S.,A+ Network | Nwaka S.,World Health Organization | Ochem A.,A+ Network | Ochem A.,World Health Organization | And 18 more authors.
BMC International Health and Human Rights | Year: 2012

A pool of 38 pan-African Centres of Excellence (CoEs) in health innovation has been selected and recognized by the African Network for Drugs and Diagnostics Innovation (ANDI), through a competitive criteria based process. The process identified a number of opportunities and challenges for health R&D and innovation in the continent: i) it provides a direct evidence for the existence of innovation capability that can be leveraged to fill specific gaps in the continent; ii) it revealed a research and financing pattern that is largely fragmented and uncoordinated, and iii) it highlights the most frequent funders of health research in the continent. The CoEs are envisioned as an innovative network of public and private institutions with a critical mass of expertise and resources to support projects and a variety of activities for capacity building and scientific exchange, including hosting fellows, trainees, scientists on sabbaticals and exchange with other African and non-African institutions. © 2012Nwaka et al.; licensee BioMed Central Ltd. Source

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