Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for Drug Design.
Selenium is traditionally considered as an antioxidant element and selenium compounds are often discussed in the context of chemoprevention and therapy. Recent studies, however, have revealed a rather more colorful and diverse biological action of selenium-based compounds, including the modulation of the intracellular redox homeostasis and an often selective interference with regulatory cellular pathways. Our basic activity and mode of action studies with simple selenium and tellurium salts in different strains of Staphylococcus aureus (MRSA) and Saccharomyces cerevisiae indicate that such compounds are sometimes not particularly toxic on their own, yet enhance the antibacterial potential of known antibiotics, possibly via the bioreductive formation of insoluble elemental deposits. Whilst the selenium and tellurium compounds tested do not necessarily act via the generation of Reactive Oxygen Species (ROS), they seem to interfere with various cellular pathways, including a possible inhibition of the proteasome and hindrance of DNA repair. Here, organic selenides are considerably more active compared to simple salts. The interference of selenium (and tellurium) compounds with multiple targets could provide new avenues for the development of effective antibiotic and anticancer agents which may go well beyond the traditional notion of selenium as a simple antioxidant.
Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1, Saarbruecken D-66123, Germany. ethiene.castellucciestevam@uni-saarland.de.
Ethiene Castellucci
EC
Estevam
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland. karolawitek.poczta@interia.pl.
Karolina
K
Witek
Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1, Saarbruecken D-66123, Germany. lisa.faulstich@uni-saarland.de.
Lisa
L
Faulstich
Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1, Saarbruecken D-66123, Germany. jawad.nasim@uni-saarland.de.
Muhammad Jawad
MJ
Nasim
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland. glatacz@cm-uj.krakow.pl.
Gniewomir
G
Latacz
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland. enrique.dominguez.alvarez@uj.edu.pl.
Enrique
E
Domínguez-Álvarez
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland. mfkonono@cyf-kr.edu.pl.
Katarzyna
K
Kieć-Kononowicz
Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo 05503-001, Brazil. marimasi@butantan.gov.br.
Marilene
M
Demasi
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland. j.handzlik@uj.edu.pl.
Jadwiga
J
Handzlik
Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1, Saarbruecken D-66123, Germany. c.jacob@mx.uni-saarland.de.
Claus
C
Jacob
D000890:Anti-Infective Agents / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018011:Chalcogens / Q000494:pharmacology; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D016566:Organoselenium Compounds / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D061988:Proteasome Inhibitors / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D012492:Salts / Q000494:pharmacology*; D012643:Selenium / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects; D013691:Tellurium / Q000494:pharmacology*
D000890:Anti-Infective Agents; D018011:Chalcogens; D016566:Organoselenium Compounds; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D012492:Salts; D012643:Selenium; D013691:Tellurium
MRSA; ROS; cellular thiolstat; proteasome; redox modulation; resistant bacteria; selenium; tellurium; yeast