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Molecules 2015, 20(8), 13894-13912; doi:10.3390/molecules200813894

Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for Drug Design

1
Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1, Saarbruecken D-66123, Germany
2
Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland
3
Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo 05503-001, Brazil
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Thomas G. Back
Received: 30 April 2015 / Revised: 14 July 2015 / Accepted: 22 July 2015 / Published: 31 July 2015
(This article belongs to the Special Issue Selenium Catalysts and Antioxidants)
View Full-Text   |   Download PDF [1468 KB, uploaded 31 July 2015]   |  

Abstract

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. View Full-Text
Keywords: cellular thiolstat; MRSA; proteasome; redox modulation; resistant bacteria; ROS; selenium; tellurium; yeast cellular thiolstat; MRSA; proteasome; redox modulation; resistant bacteria; ROS; selenium; tellurium; yeast
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Estevam, E.C.; Witek, K.; Faulstich, L.; Nasim, M.J.; Latacz, G.; Domínguez-Álvarez, E.; Kieć-Kononowicz, K.; Demasi, M.; Handzlik, J.; Jacob, C. Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for Drug Design. Molecules 2015, 20, 13894-13912.

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