Antitumor effect of chiral organotelluranes elicited in a murine melanoma model

Paschoalin, Thaysa; Martens, Adam Arai; Omori, Álvaro T.; Pereira, Felipe Valença; Juliano, Luiz; Travassos, Luiz R.; Machado-Santelli, Gláucia Maria; Cunha, Rodrigo L. O. R.

doi:10.1016/j.bmc.2019.03.032

Cited by 9 publications

(5 citation statements)

References 53 publications

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“…In that sense, 2,2′-dimethoxydiphenyl ditelluride, 2,2′-diamino-3,3′,5,5′-tetramethyldiphenyl ditelluride and 4,4′-diisopropyldiphenyl ditelluride showed anti-proliferative activities against HL-60 cells. Organotellurates also act as potential antitumor agents, by either directly inhibiting tumor cell proliferation, migration and invasion, or disrupting angiogenesis evaluated in murine melanoma model [ 26 ]. Finally, the OT compound AS101 demonstrates anti-tumor properties in vitro and in vivo , possibly due to its immunomodulatory activity [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells

et al. 2023

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Diphenyl ditelluride (DPDT) is an organotellurium (OT) compound with pharmacological properties, including antioxidant, antigenotoxic and antimutagenic activities when applied at low concentrations. However, DPDT as well as other OT compounds also show cytotoxicity against mammalian cells when treatments occur at higher drug concentrations. Considering that the underlying mechanisms of toxicity of DPDT against tumor cells have been poorly explored, the objective of our study was to investigate the effects of DPDT against both human cancer and non-tumorigenic cells. As a model, we used the colonic HCT116 cancer cells and the MRC5 fibroblasts. Our results showed that DPDT preferentially targets HCT116 cancer cells when compared to MRC5 cells with IC 50 values of 2.4 and 10.1 μM, respectively. This effect was accompanied by the induction of apoptosis and a pronounced G2/M cell cycle arrest in HCT116 cells. Furthermore, DPDT induces DNA strand breaks at concentrations below 5 μM in HCT116 cells and promotes the occurrence of DNA double strand breaks mostly during S-phase as measured by γ-H2AX/EdU double staining. Finally, DPDT forms covalent complexes with DNA topoisomerase I, as observed by the TARDIS assay, with a more prominent effect observed in HCT116 than in MRC5 cells. Taken together, our results show that DPDT preferentially targets HCT116 colon cancer cells likely through DNA topoisomerase I poisoning. This makes DPDT an interesting molecule for further development as an anti-proliferative compound in the context of cancer.

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Section: Introductionmentioning

confidence: 99%

Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells

et al. 2023

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“…Synthetic organo-chalcogeniuns have been described as promising bioactive compounds due to their important biological activities, [7] such as antiviral, [8] antioxidant [9] and antitumor activity. [7][8][9][10] Organocalcogen compounds present in their molecular structure elements from the group 16 of the periodic table, such as Selenium (Se), Tellurium (Te) and Sulfur (S). Among them, Tellurium-containing compounds have been shown to possess several interesting bioactive properties, such as immunomodulatory [11] antioxidant, [12] and anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

“…Organotellurium have particularly aroused great interest in the scientific community due to their biological properties and use in organic synthesis as intermediate agents. Synthetic organochalcogeniuns have been described as promising bioactive compounds due to their important biological activities, [7] such as antiviral, [8] antioxidant [9] and antitumor activity [7–10] . Organocalcogen compounds present in their molecular structure elements from the group 16 of the periodic table, such as Selenium (Se), Tellurium (Te) and Sulfur (S).…”

Section: Introductionmentioning

confidence: 99%

Chiral β‐arylchalcogenium azide induce apoptosis and regulate Oxidative Damage on Human Bladder Cancer Cells

et al. 2022

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In the present study, we aimed to evaluate the cytotoxic effect of chiral β-Aryl-chalcogenium azide compounds in vitro against the human bladder cancer cell line 5637. The cell growth inhibition was evaluated by MTT assay. The apoptosis induction and cellular viability were measured by DAPI staining and live/ dead assay, respectively. Also, gene expression of pro-apoptotic, anti-apoptotic and oxidative stress pathways were investigated by qRT-PCR. Finally, in silico molecular docking between the compounds and proteins involved in apoptotic and cell growth pathways was performed as well. Our results showed that 5c [(S)-(2-azido-1-phenyl-3-telurophenyl)propane)] and 5j [(S)-(2-azido-1-phenyl-3-teluro-p-methoxyphenyl)-propane)] compounds presented concentration-de-pendent cytotoxicity. Apoptosis analysis showed chromatin condensation in 13 % and 20.3 % of cells treated with compounds 5 c and 5 j, respectively, compared to untreated cells (2.34 %). Moreover, 5 c increased the relative expression of p53, Caspase-3, Caspase-9, SOD and CAT genes. Meanwhile, 5 j increased the expression of p53, p21, Caspase-3, Caspase-9, Bax, SOD, CAT, GPx, GR and iNOS genes. Finally, molecular docking showed that 5 c has a binding affinity to Survivin, Bcl-XL, RSK2, SGK1, while 5 j showed binding affinity to the SGK1 protein only. These findings suggest that β-Aryl-chalcogenium azide compounds could have a potential antitumoral effect in bladder cancer cells in vitro.

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“…For decades, numerous studies revealed that the inorganic tellurane AS101 (Figure 1) is a potent inhibitor of the cysteine proteases such as papain and cathepsin B [9a,14] . From then on, several organic and inorganic hypervalent tellurium compounds were reported as successful enzyme inhibitors, including cysteine, [6g,9b–c,15] and threonine proteases (20S proteasome), [9h] and tyrosine phosphatases (PTP1B and YopH), [9f] also indicated as promising antioxidants, [4d] antimicrobial, [6c,e,16] and antitumor agents [8j] …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Mechanism Elucidation and Biological Insights of Tellurium(IV)‐Containing Heterocycles

Souza

Menezes

Garcia

et al. 2021

Chemistry A European J

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Inspired by the synthetic and biological potential of organotellurium substances, a series of five-and six-membered ring organotelluranes containing a TeÀ O bond were synthesized and characterized. Theoretical calculations elucidated the mechanism for the oxidation-cyclization processes involved in the formation of the heterocycles, consistent with chlorine transfer to hydroxy telluride, followed by a cyclization step with simultaneous formation of the new TeÀ O bond and deprotonation of the OH group. Moreover, theoretical calculations also indicated anti-diastereoisomers to be major products for two chirality center-containing compounds. Antileishmanial assays against Leishmania amazonensis promastigotes disclosed 1,2λ 4 -oxatellurane LQ50 (IC 50 = 4.1 � 1.0; SI = 12), 1,2λ 4 -oxatellurolane LQ04 (IC 50 = 7.0 � 1.3; SI = 7) and 1,2λ 4 -benzoxatellurole LQ56 (IC 50 = 5.7 � 0.3; SI = 6) as more powerful and more selective compounds than the reference, being up to four times more active. A stability study supported by 125 Te NMR analyses showed that these heterocycles do not suffer structural modifications in aqueousorganic media or at temperatures up to 65 °C.

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Antitumor effect of chiral organotelluranes elicited in a murine melanoma model

Cited by 9 publications

References 53 publications

Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells

Diphenyl ditelluride anticancer activity and DNA topoisomerase I poisoning in human colon cancer HCT116 cells

Chiral β‐arylchalcogenium azide induce apoptosis and regulate Oxidative Damage on Human Bladder Cancer Cells

Synthesis, Mechanism Elucidation and Biological Insights of Tellurium(IV)‐Containing Heterocycles

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