Mániková Dominika, Letavayová Lucia Medvecová, Vlasáková Danuša, Košík Pavol, Estevam Ethiene Castellucci, Nasim Muhammad Jawad, Gruhlke Martin, Slusarenko Alan, Burkholz Torsten, Jacob Claus, Chovanec Miroslav
Department of Genetics, Cancer Research Institute, Vlárska 7, 833 91 Bratislava, Slovakia.
Department of Oncology, Cancer Research Institute, Vlárska 7, 833 91 Bratislava, Slovakia.
Molecules. 2014 Aug 13;19(8):12258-79. doi: 10.3390/molecules190812258.
Redox-modulating compounds derived from natural sources, such as redox active secondary metabolites, are currently of considerable interest in the field of chemoprevention, drug and phytoprotectant development. Unfortunately, the exact and occasionally even selective activity of such products, and the underlying (bio-)chemical causes thereof, are often only poorly understood. A combination of the nematode- and yeast-based assays provides a powerful platform to investigate a possible biological activity of a new compound and also to explore the "redox link" which may exist between its activity on the one side and its chemistry on the other. Here, we will demonstrate the usefulness of this platform for screening several selenium and tellurium compounds for their activity and action. We will also show how the nematode-based assay can be used to obtain information on compound uptake and distribution inside a multicellular organism, whilst the yeast-based system can be employed to explore possible intracellular mechanisms via chemogenetic screening and intracellular diagnostics. Whilst none of these simple and easy-to-use assays can ultimately substitute for in-depth studies in human cells and animals, these methods nonetheless provide a first glimpse on the possible biological activities of new compounds and offer direction for more complicated future investigations. They may also uncover some rather unpleasant biochemical actions of certain compounds, such as the ability of the trace element supplement selenite to induce DNA strand breaks.
源自天然来源的氧化还原调节化合物,如氧化还原活性次生代谢物,目前在化学预防、药物和植物保护剂开发领域备受关注。不幸的是,此类产品的确切活性,甚至偶尔的选择性活性,以及其潜在的(生物)化学原因,往往了解甚少。基于线虫和酵母的检测方法相结合,为研究新化合物的可能生物活性以及探索其活性与化学性质之间可能存在的“氧化还原联系”提供了一个强大的平台。在此,我们将展示该平台在筛选几种硒和碲化合物的活性及作用方面的实用性。我们还将展示基于线虫的检测方法如何用于获取多细胞生物体内化合物摄取和分布的信息,而基于酵母的系统可用于通过化学遗传学筛选和细胞内诊断来探索可能的细胞内机制。虽然这些简单易用的检测方法都无法最终替代在人类细胞和动物中的深入研究,但这些方法 nonetheless 能让我们初步了解新化合物的可能生物活性,并为未来更复杂的研究提供方向。它们还可能揭示某些化合物相当令人不快的生化作用,比如微量元素补充剂亚硒酸盐诱导 DNA 链断裂的能力。