LabSelen-NanoBio - Departamento de Química, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Molecular and Cellular Oncology Group, Graduate Program in Biotechnology, Universidade Federal de Pelotas, Pelotas, Brazil.
Curr Med Chem. 2023;30(21):2449-2462. doi: 10.2174/0929867329666220906095438.
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.
Antiretroviral therapy induces oxidative stress. Based on this, this manuscript's main objective is to prepare compounds that combine anti-HIV and antioxidant activities.
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.
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.
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.
本研究介绍了新的 5'-羟基-3-（杂环三唑基）-胸苷的合成和多靶点行为，以及这些化合物作为抗氧化剂和抗 HIV 药物的生物学评价。
抗逆转录病毒疗法会引起氧化应激。基于此，本文的主要目的是制备兼具抗 HIV 和抗氧化活性的化合物。
通过铜催化的 Huisgen 1,3-偶极环加成反应，利用 AZT 的叠氮基团和杂环炔烃，从市售的 AZT 制备化合物。
通过点击化学，以良好的产率得到了硫代、硒代和碲代的 AZT 衍生物。所评价的化合物具有抗氧化和抗 HIV 活性。此外，还评估了这类化合物的体内毒性。与对照组小鼠相比，代表性核苷对其生存、行为、生化肝或肾标志物没有改变。
数据表明，用简单的有机卤代片段修饰 AZT 核是可行的，通过 1,3-偶极 Huisgen 环加成反应探索叠氮基团的反应性。这些新化合物的设计显示了最初期望的生物活性。
