Chalcogenium-AZT Derivatives: A Plausible Strategy To Tackle The RT-Inhibitors-Related Oxidative Stress While Maintaining Their Anti- HIV Properties.

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.

Synthesis, antioxidant and antitumoral activities of 5'-arylchalcogeno-3-aminothymidine (ACAT) derivatives.

This article presents the preparation and in vitro biological activities of new 5'-arylchalcogeno-3-aminothymidine derivatives as antioxidants (inhibition of lipid peroxidation, scavenging of the free radical 2,2-diphenylpicrylhydrazyl and demonstration of a thiol peroxidase-like activity) as well as antitumoral agents against bladder carcinoma 5637. The chalcogeno-aminothymidines presented prominent activity in the tests for both biological properties, showing a direct relation with the chalcogenium atom.