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.