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

Molecules

Ethiene Castellucci Estevam¹  Karolina Witek²  Lisa Faulstich¹  Muhammad Jawad Nasim¹  Gniewomir Latacz²  Enrique Domínguez-Álvarez²  Katarzyna Kieć-Kononowicz²  Marilene Demasi³  Jadwiga Handzlik²  Claus Jacob¹ 

[1] Bioorganic Chemistry, Department of Pharmacy, Saarland University, Campus B2 1, Saarbruecken D-66123, Germany; E-Mails:;Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University-Medical College, ul. Medyczna 9, Cracow 30-688, Poland; E-Mails:;Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo 05503-001, Brazil; E-Mail:

关键词: cellular thiolstat;    MRSA;    proteasome;    redox modulation;    resistant bacteria;    ROS;    selenium;    tellurium;    yeast;   

DOI  :  10.3390/molecules200813894

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.