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BACKGROUND: This study presents the synthesis and multi-target behavior of the new 5'-hydroxy-3-(chalcogenyl-triazoyl)-thymidine and the biological evaluation of these compounds as antioxidant and anti-HIV agents. OBJECTIVE: Antiretroviral therapy induces oxidative stress. Based on this, this manuscript's main objective is to prepare compounds that combine anti-HIV and antioxidant activities. METHODS: The compounds were prepared from commercially available AZT through a copper-catalyzed Huisgen 1,3-dipolar cycloaddition exploiting the AZT azide group and chalcogenyl alkynes. RESULTS: The chalcogenium-AZT derivatives were obtained in good yields via click chemistry. The compounds evaluated showed antioxidant and anti-HIV activity. Additionally, in vivo toxicity of this class of compounds was also evaluated. The representative nucleoside did not change the survival, behavior, biochemical hepatic, or renal markers compared to the control mice. CONCLUSION: Data suggest the feasibility of modifying the AZT nucleus with simple organohalogen fragments, exploring the reactivity of the azide group via 1,3-dipolar Huisgen cycloaddition reaction. The design of these new compounds showed the initially desired biological activities.

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Organoselenium compounds have been successfully applied in biological, medicinal and material sciences, as well as a powerful tool for modern organic synthesis, attracting the attention of the scientific community. This great success is mainly due to the breaking of paradigm demonstrated by innumerous works, that the selenium compounds were toxic and would have a potential impact on the environment. In this update review, we highlight the relevance of these compounds in several fields of research as well as the possibility to synthesize them through more environmentally sustainable methodologies, involving catalytic processes, flow chemistry, electrosynthesis, as well as by the use of alternative energy sources, including mechanochemical, photochemistry, sonochemical and microwave irradiation.

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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 Saccharomyces cerevisiae. Cell growth of S. cerevisiae 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 S. cerevisiae is time and concentration dependent, presenting more toxicity when compared with PhSeZnCl.

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A simple and efficient protocol to prepare divinyl selenides has been developed by the regio- and stereoselective addition of sodium selenide species to aryl alkynes. The nucleophilic species was generates in situ, from the reaction of elemental selenium with NaBH4, utilizing PEG-400 as the solvent. Several divinyl selenides were obtained in moderate to excellent yields with selectivity for the (Z,Z)-isomer by a one-step procedure that was carried out at 60 °C in short reaction times. The methodology was extended to tellurium, giving the desired divinyl tellurides in good yields. Furthermore, the Fe-catalyzed cross-coupling reaction of bis(3,5-dimethoxystyryl) selenide 3f with (4-methoxyphenyl)magnesium bromide 5 afforded resveratrol trimethyl ether 6 in 57% yield.

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The antioxidant properties of organoselenium compounds have been extensively investigated with the aim of developing new drugs, since oxidative stress is responsible for a variety of chronic human diseases. Herein, we reported the synthesis of new nitrogen-containing diselenides by a simple and efficient synthetic route. The products were obtained in good to excellent yields and their identification and characterization were achieved by NMR and HRMS techniques. The new derivatives may represent promising structures with different biological activities, which can act against oxidative stress through diverse mechanisms of action. The glutathione peroxidase-like assay (GPx-like activity) of the new synthesized compounds indicated that they reduced H2O2 to water at the expense of PhSH. The best results were obtained with diselenide 2b, which was 9 times more active than the standard organoselenium drug ebselen and, in contrast, this compound was not reduced by hepatic TrxR. All of the new compounds inhibited Fe(II)-induced TBARS.

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