Selenium‐ and Tellurium‐Containing Multifunctional Redox Agents as Biochemical Redox Modulators with Selective Cytotoxicity

Abstract

Various human diseases, including different types of cancer, are associated with a disturbed intracellular redox balance and oxidative stress (OS). The past decade has witnessed the emergence of redox-modulating compounds able to utilize such pre-existing disturbances in the redox state of sick cells for therapeutic advantage. Selenium- and tellurium-based agents turn the oxidizing redox environment present in certain cancer cells into a lethal cocktail of reactive species that push these cells over a critical redox threshold and ultimately kill them through apoptosis. This kind of toxicity is highly selective: normal, healthy cells remain largely unaffected, since changes to their naturally low levels of oxidizing species produce little effect. To further improve selectivity, multifunctional sensor/effector agents are now required that recognize the biochemical signature of OS in target cells. The synthesis of such compounds provides interesting challenges for chemistry in the future.

Metal, Metalloid, and Oxide Nanoparticles for Therapeutic and Diagnostic Oncology

“…However, interaction of selenium with intracellular proteins such as glutathione peroxidase (Gpx), superoxide dismutase (SOD) or catalase, and any other enzymes that have cysteine in their active site and inhibition of their activity results in the accumulation of ROS in the cell cytoplasm [212]. Therefore, considering the higher level of these enzymes in cancer cells due to the higher level of metabolism and mitochondrial respiration, an optimum dose of selenium may cause more toxicity for cancer cells compared to normal cells.…”

Targeting the disturbed redox equilibrium in chronic lymphocytic leukemia by novel reactive oxygen species-catalytic ‘sensor/effector’ compounds

“…Here, we report on a novel principle to exploit the disturbed redox regulation by a class of organochalcogen-based ROS catalysts [8]. The design of such compounds to potentiate tumor-associated high-level ROS toward toxic levels [ Figure 1(A)] contrasts with other redox-based targeting approaches.…”

New Selenoderivatives as Antitumoral Agents

“…Se based agents (Figure 6) turn the oxidizing redox environment present in certain cancer cells into a lethal cocktail of reactive species that push these cells over a critical redox threshold and ultimately kill them through apoptosis. The main advantage is that this kind of toxicity is highly selective: normal, healthy cells remain largely unaffected, since changes to their naturally low levels of oxidizing species produce little effect though the biochemical pathways triggered by these agents need to be studied in more detail such as redox modulator like cysteine-containing Bcl proteins, which control apoptosis at an early stage, certain caspases, which execute apoptotic mechanisms further downstream, are also redox sensitive (Jamier et al, 2010). …”