Induction of reactive oxygen species by diphenyl diselenide is preceded by changes in cell morphology and permeability in <i>Saccharomyces cerevisiae</i>

<p>Organoselenium compounds, such as diphenyl diselenide (PhSe)₂ and phenylselenium zinc chloride (PhSeZnCl), show protective activities related to their thiol peroxidase activity. However, depending on experimental conditions, organoselenium compounds can cause toxicity by oxidising thiol groups of proteins and induce the production of reactive oxygen species (ROS). Here, we analysed the toxicity of (PhSe)₂ and PhSeZnCl in yeast <i>Saccharomyces cerevisiae</i>. Cell growth of <i>S. cerevisiae</i> after 1, 2, 3, 4, 6, and 16 h of treatment with 2, 4, 6, and 10 μM of (PhSe)₂ was evaluated. For comparative purpose, PhSeZnCl was analysed only at 16 h of incubation at equivalent concentrations of selenium (i.e. 4, 8, 12, and 20 μM). ROS production (DCFH-DA), size, granularity, and cell membrane permeability (propidium iodide) were determined by flow cytometry. (PhSe)₂ inhibited cell growth at 2 h (10 μM) of incubation, followed by increase in cell size. The increase of cell membrane permeability and granularity (10 μM) was observed after 3 h of incubation, however, ROS production occurs only at 16 h of incubation (10 μM) with (PhSe)₂, indicating that ROS overproduction is a more likely consequence of (PhSe)₂ toxicity and not its determinant. All tested parameters showed that only concentration of 20 μM induced toxicity in samples incubated with PhSeZnCl. In summary, the results suggest that (PhSe)₂ toxicity in <i>S. cerevisiae</i> is time and concentration dependent, presenting more toxicity when compared with PhSeZnCl.</p

New Organochalcogen Multitarget Drug: Synthesis and Antioxidant and Antitumoral Activities of Chalcogenozidovudine Derivatives

In this article we present the synthesis, characterization, and in vitro biological and biochemical activities of new chalcogenozidovudine derivatives as antioxidant (inhibition of TBARS in brain membranes and thiol peroxidase-like activity) as well as antitumoral agents in bladder carcinoma 5637. A prominent response was obtained for the selected chalcogenonucleosides, showing effective antioxidant and antitumoral activities