Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for Drug Design.
Aspects of a Distinct Cytotoxicity of Selenium Salts and Organic Selenides in Living Cells with Possible Implications for Drug Design.
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DOI：
10.3390/molecules200813894
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发表时间：
2015-07-31
期刊：
影响因子：
--
通讯作者：
Jacob C
中科院分区：
文献类型：
--
作者：
Estevam EC;Witek K;Faulstich L;Nasim MJ;Latacz G;Domínguez-Álvarez E;Kieć-Kononowicz K;Demasi M;Handzlik J;Jacob C
传统上，硒被认为是一种抗氧化元素，硒化合物经常在化学预防和治疗的背景下讨论。然而，最近的研究揭示了硒基化合物的更加丰富多彩的生物作用，包括调节细胞内氧化还原稳态以及通常选择性干扰调节性细胞途径。我们对不同菌株的金黄色葡萄球菌 (MRSA) 和酿酒酵母中的简单硒盐和碲盐进行的基本活性和作用方式研究表明，这些化合物有时本身并没有特别的毒性，但可能通过生物还原形成不溶性元素沉积物来增强已知抗生素的抗菌潜力。虽然测试的硒和碲化合物不一定通过产生活性氧 (ROS) 发挥作用，但它们似乎会干扰各种细胞途径，包括可能抑制蛋白酶体和阻碍 DNA 修复。与简单盐相比，有机硒化物的活性要高得多。硒（和碲）化合物对多个靶点的干扰可以为开发有效的抗生素和抗癌药物提供新途径，这可能远远超出硒作为简单抗氧化剂的传统概念。
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.
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影响因子：
13.6
作者：
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