New 3’‐Triazolyl‐5’‐aryl‐chalcogenothymidine: Synthesis and Anti‐oxidant and Antiproliferative Bladder Carcinoma (5637) Activity

München, Taiana S.; Sonego, Mariana Souza; Souza, Diego de; Dornelles, Luciano; Seixas, Fabiana Kömmling; Collares, Tiago; Piccoli, Bruna Candia; Silva, Fernanda D’Avila da; Rocha, João Batista Teixeira da; Quoos, Natália; Rodrigues, Oscar E. D.

doi:10.1002/slct.201800156

Cited by 10 publications

(4 citation statements)

References 37 publications

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“…Selenium compounds have shown anti-cancer effects especially based on production of reactive species of oxygen (ROS) and chromatin modification ( 27 ). Induction of apoptosis mediated by the combination of AZT with elements chalcogenides is considered a promising strategy for chemopreventive agents ( 9 , 10 ). In this context, the present study demonstrated the effect of AZT and derivatives in breast tumor cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…3′-Azido-3′-deoxythymidine (AZT) is a nucleoside analog used in the treatment of acquired immunodeficiency syndrome (AIDS) due to its antiretroviral activity, however it was firstly developed as an anti-cancer agent ( 6 ). Anti-neoplasic potential of AZT has been shown for several tumor cell lines, including those derived from colon ( 7 ), breast ( 8 ), bladder ( 9 , 10 ), and esophageal ( 11 ) cancers.…”

Section: Introductionmentioning

confidence: 99%

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Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line

et al. 2018

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Triple-negative breast cancer represents about 15% of all cases of breast cancer, and still represents a therapeutic challenge. 3′-Azido-3′-deoxythymidine (AZT) is a nucleoside reverse transcriptase inhibitor with antitumor activity. Chalcogenides compounds, such as selenium, are very important intermediates applied in organic synthesis. Our objective was to investigate the effect and the underlying cell death mechanisms of AZT and its derivatives, in human breast cancer cell lines. The inhibitory effect of AZT and derivatives (1072, 1073, and 1079) was determined by MTT assay (0.1, 1, 10, 50, and 100 μM for concentrations and times 4, 24, 48, and 72 h) and Live/Dead in tumor cell lines MCF-7, MDA-MB 231 and also in non-tumor cell line CHO. Gene expression profiles related to apoptosis were investigated by qRT-PCR and induction of apoptosis was investigated by flow cytometry. MTT and Live/Dead assays showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 50 and 100 μM in tumor cell lines MCF-7 and MDA-MB 231 while the commercial AZT presented a low antitumoral potential in all strains tested. In flow cytometry analysis we demonstrated that derivatives of AZT induced apoptosis, with an increase in both initial and late stages in both tumor cell lines evaluated, especially in MDA-MB 231. Our data show that the AZT derivative 1072 increased the expression of transcripts of the genes caspase 3 and 8 in MDA-MB 231 cell line when compared to control, suggesting that the extrinsic pathway of apoptosis was activated. In conclusion, derivatives of AZT, especially 1072, induce cytotoxicity in vitro in the triple negative breast cancer cell line through activation of the extrinsic pathway of apoptosis. These compounds containing selenium in its formulation are potential therapeutic agents for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line

et al. 2018

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“…Regarding its detrimental drawbacks, great efforts have been made to circumvent them and improve their effectiveness and safety. Thereby, several chalcogenozidovudine derivatives have been synthesized, and their potential pharmacological properties have been reported. ,,− Of note, Sebcontaining AZT analogues have attracted prominent attention as Se levels are decreased in HIV-positive patients and its supplementation has been suggested as a feasible approach to ameliorate the detrimental outcomes of this infection. , Regarding the design of the novel compounds, it was expected that the replacement of the hydroxyl group located in the 5′ position of the deoxyribose ring with different phenylseleno moieties could lead to increased lipophilicity of the derivatives. For didactic purposes, the most representative Se-AZT derivatives have been compiled in Figure , and we have encompassed a plethora of articles that support the interesting therapeutic role of the most representative compound.…”

Section: Selenized Small Molecule Drugsmentioning

confidence: 99%

Selenization of Small Molecule Drugs: A New Player on the Board

Morán-Serradilla,

Plano,

Sanmartín

et al. 2024

J. Med. Chem.

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There is an urgent need to develop safer and more effective modalities for the treatment of a wide range of pathologies due to the increasing rates of drug resistance, undesired side effects, poor clinical outcomes, etc. Throughout the years, selenium (Se) has attracted a great deal of attention due to its important role in human health. Besides, a growing body of work has unveiled that the inclusion of Se motifs into a great number of molecules is a promising strategy for obtaining novel therapeutic agents. In the current Perspective, we have gathered the most recent literature related to the incorporation of different Se moieties into the scaffolds of a wide range of known drugs and their feasible pharmaceutical applications. In addition, we highlight different representative examples as well as provide our perspective on Se drugs and the possible future directions, promises, opportunities, and challenges of this ground-breaking area of research. ■ SIGNIFICANCE • Significance: The development of novel compounds for the treatment of numerous pathologies has become a priority due to the lack of effective therapeutic options. • Impact: This work highlights the potential of incorporating Se moieties into the scaffold of several drugs to develop novel safer bioactive compounds. • Innovation: This Perspective discusses the development of selenoderivatives of a wide array of drugs and their biological applications and proposes novel avenues to continue exploring this outstanding research area.

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“…Furthermore, in recent years, AZT-based therapeutics have drawn significant attention because of their proven medicinal importance as HIV drugs [27], antitumor effects [28], antioxidant [29], and AZT prodrugs for anticancer and antiviral activities [30,31]. In particular, AZTs have a wide range of applications as anticancer agents that inhibit several tumor cell lines, including colon [32], breast [33], bladder [29,34], and esophageal cancers [35].…”

Section: Introductionmentioning

confidence: 99%

Amphipathic Small Molecule AZT Compound Displays Potent Inhibitory Effects in Cancer Cell Proliferation

et al. 2021

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Cancer has been identified as a leading cause of death worldwide, and the increasing number of cancer cases threatens to shorten the average life expectancy of people. Recently, we reported a 3-azido-3-deoxythymidine (AZT)-based amphipathic small molecule, ADG-2e that revealed a notable potency against tumor metastasis. To evaluate the anticancer potential of ADG-2e, we assessed its anticancer potency in vitro and in vivo. Anticancer screening of ADG-2e against cervical cancer cells, HeLa CCL2, and BT549 mammary gland ductal carcinoma showed significant inhibition of cancer cell proliferation. Furthermore, mechanistic investigations revealed that cancer cell death presumably proceeded through an oncosis mechanistic pathway because ADG-2e treated cells showed severe damage on the plasma membrane, a loss of membrane integrity, and leakage of α-tubulin and β-actin. Finally, evaluation of the antitumorigenic potential of ADG-2e in mouse xenograft models revealed that this compound potentially inhibits cancer cell proliferation. Collectively, these findings suggest that ADG-2e can evolve as an anticancer agent, which may represent a model for nucleoside-based small molecule anticancer drug discovery.

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New 3’‐Triazolyl‐5’‐aryl‐chalcogenothymidine: Synthesis and Anti‐oxidant and Antiproliferative Bladder Carcinoma (5637) Activity

Cited by 10 publications

References 37 publications

Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line

Revitalizing the AZT Through of the Selenium: An Approach in Human Triple Negative Breast Cancer Cell Line

Selenization of Small Molecule Drugs: A New Player on the Board

Amphipathic Small Molecule AZT Compound Displays Potent Inhibitory Effects in Cancer Cell Proliferation

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