Evaluation of the effect of synthetic compounds derived from azidothymidine on MDA-MB-231 type breast cancer cells

Rocha, Adriely Maria Oliveira; Sousa, Fernanda Severo Sabedra; Borba, Victoria Mascarenhas; München, Taiana S.; Leal, Julliano Guerin; Rodrigues, Oscar E. D.; Fronza, Mariana G.; Savegnago, Lucielli; Collares, Tiago; Seixas, Fabiana Kömmling

doi:10.1016/j.bmcl.2020.127365

Cited by 5 publications

(4 citation statements)

References 28 publications

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“…The effect of CFE, IR-CFE, and IR on cell viability was measured by MTT assay according to the method reported previously with slight modifications (Rocha et al, 2020). The AML-12 cells (4 × 10 3 cells/well) were placed into 96-well plates.…”

Section: In Vitro Experimentsmentioning

confidence: 99%

Radioprotective effect of radiation-induced Lactococcus lactis cell-free extract against 60Coγ injury in mice

Suo

Chen

Xue

et al. 2021

Journal of Dairy Science

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Ionizing radiation (IR) is widely used in the diagnosis and treatment of various cancers. However, IR can cause damage to human health by producing reactive oxygen species. Lactococcus lactis is a type of microorganism that is beneficial to human health and has a strong antioxidant capacity. In this study, the protective effect of normal and IR-induced L. lactis IL1403 cell-free extracts (CFE and IR-CFE, respectively) against oxidative damage in vitro and the radioprotective effect of IR-CFE in vivo was evaluated using 60 Coγ-induced oxidative damage model in mice. Results showed that IR-CFE exhibited a stronger oxidative damage-protective effect than CFE for L. lactis IL1403 under H 2 O 2 in vitro. Moreover, IR-CFE also showed strong radioprotective effect on hepatocyte cells (AML-12) under radiation condition, and the effect was better than that of CFE. Animal experiment indicated that IR-CFE could reduce the IR-induced damage to the hematopoietic system by increasing the number of white blood cells and red blood cells in peripheral blood of irradiated mice. It was also observed that IR-CFE could markedly alleviate the 60 Coγ-induced oxidative stress via increasing the activities of superoxide dismutase and glutathione peroxidase, enhancing the levels of glutathione, and decreasing the contents of malondialdehyde in serum, liver, and spleen. In addition, IR-CFE also could reduce the activities of alanine transaminase and aspartate aminotransferase in serum, thereby reducing radiation damage to the liver. These results suggested that IR-CFE could be considered as potential candidates for natural radioprotective agents. This study provides a theoretical basis for improving the application of lactic acid bacteria.

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Section: In Vitro Experimentsmentioning

confidence: 99%

Radioprotective effect of radiation-induced Lactococcus lactis cell-free extract against 60Coγ injury in mice

Suo

Chen

Xue

et al. 2021

Journal of Dairy Science

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“…The performance of organoselenium, organotellurium, and organosulfur against free radicals, as well as their effectiveness as antiviral, anti-inflammatory, and antitumor agents, has directed many scientific studies [ 72 , 73 , 74 ]. Rocha et al [ 46 ], in their research on breast cancer, considered that AZT combined with tellurium not only exhibited selectivity between cancerous and healthy cells, but also had a good pharmacokinetic profile and efficient protective action against oxidative stress. Furthermore, in the study with derivatives of 3′-triazolyl-5′-arylchalcogenilthymidine containing tellurium, it was observed that the higher reactivity and electron-donating capacity presented by this chalcogen justified its better anti-proliferative performance under bladder carcinoma 5637 cells, and, contrary to expectations, tellurium compounds were less toxic in human cell lines and rodents than selenium compounds [ 75 ].…”

Section: Resultsmentioning

confidence: 99%

“…Previous data from the group have demonstrated that new compounds formed by adding chalcogen atoms to the structure of commercial AZT were able to enhance the in vitro antioxidant and antitumor action of the hydride molecules [ 46 , 47 ]. In this context, it was reported that the presence of chalcogen in the molecule 5′-arylchalcogenyl-3-(phenylselanyl-triazoyl)-thymidine reduced the proliferative capacity of bladder cancer cells and amplified the activity of the compound [ 48 ].…”

Section: Introductionmentioning

confidence: 99%

“…In this context, it was reported that the presence of chalcogen in the molecule 5′-arylchalcogenyl-3-(phenylselanyl-triazoyl)-thymidine reduced the proliferative capacity of bladder cancer cells and amplified the activity of the compound [ 48 ]. Additional results revealed that in breast cancer cell line, AZT analogs containing tellurium were more effective in inhibiting tumor growth and showed lower cytotoxicity than the original antiretroviral molecule [ 46 ]. Furthermore, it was described that the organochalcogen 5′-selenothymidine (S1073) acts as an important neuroprotective agent and attenuates oxidative stress in mice with cognitive dysfunction induced by intracerebroventricular-streptozotocin (ICV-STZ) [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

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Antiviral Effect of 5′-Arylchalcogeno-3-aminothymidine Derivatives in SARS-CoV-2 Infection

Tucci,

da Rosa,

Rosa

et al. 2023

Molecules

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The understanding that zidovudine (ZDV or azidothymidine, AZT) inhibits the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 and that chalcogen atoms can increase the bioactivity and reduce the toxicity of AZT has directed our search for the discovery of novel potential anti-coronavirus compounds. Here, the antiviral activity of selenium and tellurium containing AZT derivatives in human type II pneumocytes cell model (Calu-3) and monkey kidney cells (Vero E6) infected with SARS-CoV-2, and their toxic effects on these cells, was evaluated. Cell viability analysis revealed that organoselenium (R3a–R3e) showed lower cytotoxicity than organotellurium (R3f, R3n–R3q), with CC50 ≥ 100 µM. The R3b and R3e were particularly noteworthy for inhibiting viral replication in both cell models and showed better selectivity index. In Vero E6, the EC50 values for R3b and R3e were 2.97 ± 0.62 µM and 1.99 ± 0.42 µM, respectively, while in Calu-3, concentrations of 3.82 ± 1.42 µM and 1.92 ± 0.43 µM (24 h treatment) and 1.33 ± 0.35 µM and 2.31 ± 0.54 µM (48 h) were observed, respectively. The molecular docking calculations were carried out to main protease (Mpro), papain-like protease (PLpro), and RdRp following non-competitive, competitive, and allosteric inhibitory approaches. The in silico results suggested that the organoselenium is a potential non-competitive inhibitor of RdRp, interacting in the allosteric cavity located in the palm region. Overall, the cell-based results indicated that the chalcogen-zidovudine derivatives were more potent than AZT in inhibiting SARS-CoV-2 replication and that the compounds R3b and R3e play an important inhibitory role, expanding the knowledge about the promising therapeutic capacity of organoselenium against COVID-19.

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Chalcogen-containing Protein and Nucleic Acid Derivatives – Synthesis and Applications

Iwaoka

2023

Chalcogen Chemistry: Fundamentals and Applications

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Chalcogen analogues, which are synthetic derivatives of natural proteins or nucleic acids with a substitution of sulfur (S), selenium (Se), or tellurium (Te) at any specific positions, show unique biological activities different from the original biomolecules, thus stimulating interest of researchers and anticipating various applications. In this chapter, after briefly providing an overview of chalcogen-containing natural proteins and nucleic acids, recent advances in the chemical synthesis as well as the assessments of unique biological properties of chalcogen analogues are summarized, giving some notable examples.

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Evaluation of the effect of synthetic compounds derived from azidothymidine on MDA-MB-231 type breast cancer cells

Cited by 5 publications

References 28 publications

Radioprotective effect of radiation-induced Lactococcus lactis cell-free extract against 60Coγ injury in mice

Radioprotective effect of radiation-induced Lactococcus lactis cell-free extract against 60Coγ injury in mice

Antiviral Effect of 5′-Arylchalcogeno-3-aminothymidine Derivatives in SARS-CoV-2 Infection

Chalcogen-containing Protein and Nucleic Acid Derivatives – Synthesis and Applications

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