Cancer molecular biology and strategies for the design of cytotoxic gold(i) and gold(iii) complexes:a tutorial review

Abstract This tutorial review highlights key principles underpinning the design of selected metallodrugs to target specific biological macromolecules (DNA and proteins). The review commences with a descriptive overview of the eukaryotic cell cycle and the molecular biology of cancer, particularly apoptosis, which is provided as a necessary foundation for the discovery, design, and targeting of metal-based anticancer agents. Drugs which target DNA have been highlighted and clinically approved metallodrugs discussed. A brief history of the development of mainly gold-based metallodrugs is presented prior to addressing ligand systems for stabilizing and adding functionality to bio-active gold(I) and gold(III) complexes, particularly in the burgeoning field of anticancer metallodrugs. Concepts such as multi-modal and selective cytotoxic agents are covered where necessary for selected compounds. The emerging role of carbenes as the ligand system of choice to achieve these goals for gold-based metallodrug candidates is highlighted prior to closing the review with comments on some future directions that this research field might follow. The latter section ultimately emphasizes the importance of understanding the fate of metal complexes in cells to garner key mechanistic insights

A cytotoxic bis(1,2,3-triazol-5-ylidene)carbazolide gold(III) complex targets DNA by partial intercalation

Abstract The syntheses of bis(triazolium)carbazole precursors and their corresponding coinage metal (Au, Ag) complexes are reported. For alkylated triazolium salts, di- or tetranuclear complexes with bridging ligands were isolated, while the bis(aryl) analogue afforded a bis(carbene) AuI-CNC pincer complex suitable for oxidation to the redox-stable [AuIII(CNC)Cl]⁺ cation. Although the ligand salt and the [AuIII(CNC)Cl]⁺ complex were both notably cytotoxic toward the breast cancer cell line MDA-MB-231, the AuIII complex was somewhat more selective. Electrophoresis, viscometry, UV-vis, CD and LD spectroscopy suggest the cytotoxic [AuIII(CNC)Cl]⁺ complex behaves as a partial DNA intercalator. In silico screening indicated that the [AuIII(CNC)Cl]⁺ complex can target DNA three-way junctions with good specificity, several other regular B-DNA forms, and Z-DNA. Multiple hydrophobic π-type interactions involving T and A bases appear to be important for B-form DNA binding, while phosphate O⋅⋅⋅Au interactions evidently underpin Z-DNA binding. The CNC ligand effectively stabilizes the AuIII ion, preventing reduction in the presence of glutathione. Both the redox stability and DNA affinity of the hit compound might be key factors underpinning its cytotoxicity in vitro

The impact of university incorporation on college lecturers

In South Africa, recent government plans to change the institutional landscape of higher education have resulted in mergers of colleges into universities or technikons. The research reported in this article focuses solely on the impact of a "college-into-university" incorporation as manifested in the personal, emotional and career experiences of these college staff members. It traces the changes in their perceptions and emotions during and after the incorporation process. It also identifies recurring themes and issues evident in the personal lives of those affected by this incorporation. A unique research methodology was engaged: The College staff who had been appointed to the university after the merger, identified seven critical themes and then designed and conducted 30 semi-structured interviews among themselves. This article thus documents the impact of incorporation into a university on the individual and collective lives of the researchers themselves. The data suggest that the emotional impact of incorporation was intense and that the uncertainty, especially, led to considerable trauma. The most important concern emanating from this joint research project is that while a certain degree of distress is unavoidable in any institutional merger, inattention to the management of human resources, emotions and aspirations could linger on, possibly having a negative effect on the ambitions for the transformation of the new entity.The original publication is available at www.springerlink.co