Intracellular Diagnostics: Hunting for the Mode of Action of Redox-Modulating Selenium Compounds in Selected Model Systems

Abstract

Redox-modulating compounds derived from natural sources, such as redox active secondary metabolites, are currently of considerable interest in the field of chemoprevention, drug and phytoprotectant development. Unfortunately, the exact and occasionally even selective activity of such products, and the underlying (bio-)chemical causes thereof, are often only poorly understood. A combination of the nematode-and yeast-based assays provides a powerful platform to investigate a possible biological activity of a new compound and also to explore the "redox link" which may exist between its activity on the one side and its chemistry on the other. Here, we will demonstrate the usefulness of this platform for screening several selenium and tellurium compounds for OPEN ACCESSMolecules 2014, 19 12259 their activity and action. We will also show how the nematode-based assay can be used to obtain information on compound uptake and distribution inside a multicellular organism, whilst the yeast-based system can be employed to explore possible intracellular mechanisms via chemogenetic screening and intracellular diagnostics. Whilst none of these simple and easy-to-use assays can ultimately substitute for in-depth studies in human cells and animals, these methods nonetheless provide a first glimpse on the possible biological activities of new compounds and offer direction for more complicated future investigations. They may also uncover some rather unpleasant biochemical actions of certain compounds, such as the ability of the trace element supplement selenite to induce DNA strand breaks.

Negative Impact of Total Body Irradiation on the Antitumor Activity of Rhenium-(I)-diselenoether

“…Not all Se compounds will have the same effect on the redox status and different flurorescent markers may be used in cells to compare them (24), e.g. 2',7'-dichlorodihydrofluorescein diacetate for the production of total ROS, knowing that this reagent mainly reacts with peroxides; MitoSOX Red to assay mitochondrial O 2…”

Crystallographic and docking (Cathepsins B, K, L and S) studies on bioactive halotelluroxetanes

“…Since the discovery of selenium as a component of glutathione peroxidase [1,2] and of the 21 st amino acid, selenocysteine [3,4], selenium compounds have been increasingly investigated as potential therapeutic agents against a range of diseases [5][6][7][8][9][10]. Due to the chemical similarities to tellurium, selenium's heavier congener, tellurium compounds have also attracted interest in the pharmaceutical context [11,12].…”

Efficacy of Allicin against Plant Pathogenic Fungi and Unveiling the Underlying Mode of Action Employing Yeast Based Chemogenetic Profiling Approach

“…During chemogenetic screening, various yeast deletion strains lacking specific genes were employed and toxicity was observed in the presence of the drug with reference to the wildtype. The mutants that are hypersensitive to drugs compared to the wildtype may give clue about the possible relationship between the drug and the gene for a specific protein/enzyme absent in the mutant and its role in metabolism or defense This technique is simple, easy and presents a robust avenue for the cost-effective and prompt screening of numerous compounds in order to identify the possible targets and modes of action of cytotoxic compounds [57].…”