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The global incidence of cancer is rising rapidly and continues to be one of the leading causes of death in the world. Melanoma deserves special attention since it represents one of the fastest growing types of cancer, with advanced metastatic forms presenting high mortality rates due to the development of drug resistance. The aim of this review is to evaluate how the screening of drugs and compounds for melanoma has been performed over the last seven decades. Thus, we performed literature searches to identify melanoma drug screening methods commonly used by research groups during this timeframe. In vitro and in vivo tests are essential for the development of new drugs; however, incorporation of in silico analyses increases the possibility of finding more suitable candidates for subsequent tests. In silico techniques, such as molecular docking, represent an important and necessary first step in the screening process. However, these techniques have not been widely used by research groups to date. Our research has shown that the vast majority of research groups still perform in vitro and in vivo tests, with emphasis on the use of in vitro enzymatic tests on melanoma cell lines such as SKMEL and in vivo tests using the B16 mouse model. We believe that the union of these three approaches ( in silico, in vitro , and in vivo ) is essential for improving the discovery and development of new molecules with potential antimelanoma action. This workflow would provide greater confidence and safety for preclinical trials, which will translate to more successful clinical trials and improve the translatability of new melanoma treatments into clinical practice while minimizing the unnecessary use of laboratory animals under the principles of the 3R's.

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, the main objective of this manuscript is the preparation of 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 cycloadditions 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 and the representative nucleoside did not change the survival, behavior, biochemical hepatic, and renal markers compared to the control mice. Conclusion: Data suggest the feasibility of modifying the AZT nucleus with simple organochalcogen 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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