Selenium- and tellurium-containing multifunctional redox agents as biochemical redox modulators with selective cytotoxicity.
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.
Jamier
Vincent
V
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, Campus, 66123 Saarbruecken, Germany.
Ba
Lalla A
LA
Jacob
Claus
C
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012643:Selenium / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D013691:Tellurium / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D000975:Antioxidants; D003603:Cytotoxins; D008665:Metalloporphyrins; D012643:Selenium; D013691:Tellurium