Expression proteomics study to determine metallodrug targets and optimal drug combinations.

The emerging technique termed functional identification of target by expression proteomics (FITExP) has been shown to identify the key protein targets of anti-cancer drugs. Here, we use this approach to elucidate the proteins involved in the mechanism of action of two ruthenium(II)-based anti-cancer compounds, RAPTA-T and RAPTA-EA in breast cancer cells, revealing significant differences in the proteins upregulated. RAPTA-T causes upregulation of multiple proteins suggesting a broad mechanism of action involving suppression of both metastasis and tumorigenicity.

Vector Control in Developing Countries: Challenges and Solutions.

Undoubtedly, reducing vector populations or their interactions with hosts below a critical level is a practical and proven method of disease control. Introduction of insecticide-treated bed nets has significantly reduced malaria in some parts of the world. However, for many reasons, implementation of such strategies is challenging and the protection offered by particular products limited: bed nets are only effective during sleep.

Metal-based drugs that break the rules.

Cisplatin and other platinum compounds have had a huge impact in the treatment of cancers and are applied in the majority of anticancer chemotherapeutic regimens. The success of these compounds has biased the approaches used to discover new metal-based anticancer drugs. In this perspective we highlight compounds that are apparently incompatible with the more classical (platinum-derived) concepts employed in the development of metal-based anticancer drugs, with respect to both compound design and the approaches used to validate their utility.

Light in Medicine: The Interplay of Chemistry and Light.

Photodynamic therapy (PDT) has had mixed reception in the clinic, with most success stories being based on the ablative capacity of PDT. In these applications, maximal combinations of light and an exogenous photosensitiser are used to generate high levels of reactive oxygen species (ROS) that induce cell death either directly via necrosis or indirectly via vascular damage. However, recent advances in understanding the complex role of ROS in cell signalling have revealed potential new applications for PDT.

Light in Medicine: The Interplay of Chemistry and Light.

Photodynamic therapy (PDT) has had mixed reception in the clinic, with most success stories being based on the ablative capacity of PDT. In these applications, maximal combinations of light and an exogenous photosensitiser are used to generate high levels of reactive oxygen species (ROS) that induce cell death either directly via necrosis or indirectly via vascular damage. However, recent advances in understanding the complex role of ROS in cell signalling have revealed potential new applications for PDT.

Hydrolysis study of the bifunctional antitumour compound RAPTA-C, [Ru(eta6-p-cymene)Cl2(pta)].

The hydrolysis of [Ru(eta(6)-p-cymene)Cl(2)(PTA)] (PTA=1,3,5-triaza-7-phosphatricyclo-[3.3.1.

A mass spectrometric and molecular modelling study of cisplatin binding to transferrin.

A combination of mass spectrometry, UV/Vis spectroscopy and molecular modelling techniques have been used to characterise the interaction of cisplatin with human serum transferrin (Tf). Mass spectrometry indicates that cisplatin binds to the hydroxy functional group of threonine 457, which is located in the iron(III)-binding site on the C-terminal lobe of the protein. UV/Vis spectroscopy confirms the stoichiometry of binding and shows that cisplatin and iron(III) binding are competitive.

Rational design of platinum(IV) compounds to overcome glutathione-S-transferase mediated drug resistance.

A rationally designed Pt(IV) anticancer compound is described, employing the novel concept of tethering an inhibitor of glutathione-S-transferase, an enzyme associated with Pt-based drug-resistance, to cisplatin. Its enzyme inhibition activity, investigated using spectrophotometric and mass spectrometry-based techniques, and cytotoxic profile in resistant cancer cells are described.

Determination of drug binding sites to proteins by electrospray ionisation mass spectrometry: the interaction of cisplatin with transferrin.

Cisplatin, cis-[PtCl2(NH3)2], is known to bind to human serum transferrin, but the binding site remains a matter of some debate. Electrospray ionisation mass spectrometry has been used to characterise the interaction of cisplatin with transferrin. The studies indicate that cisplatin initially docks with, and subsequently bonds covalently to, the hydroxyl functional group of threonine 457, with the loss of HCl affording a transferrin-O-PtCl(NH3)2 adduct.