Butyltin(IV) Benzoates: Inhibition of Thioredoxin Reductase, Tumor Cell Growth Inhibition, and Interactions with Proteins

Oliveira, Kely Navakoski de; Andermark, Vincent; Grafenstein, Susanne von; Onambele, Liliane A.; Dahl, Gregor; Rubbiani, Riccardo; Wolber, Gerhard; Gabbiani, Chiara; Messori, Luigi; Prokop, Aram; Ott, Ingo

doi:10.1002/cmdc.201200505

Cited by 28 publications

(12 citation statements)

References 59 publications

(109 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Apart from 144 , the tri‐ n ‐butyltin carboxylates were weaker TrxR inhibitors than the corresponding di‐ n ‐butyl derivatives. N ‐acetylated derivatives 154–157 were more active than those with amino groups ( 142 and 151–153 , respectively) . Subsequently, they continued to report tin (IV) complexes are inhibitors of TrxR and trigger strong cytotoxicity in MCF‐7 and HT‐29 tumor cells (Table ).…”

Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Zhang

et al. 2018

Medicinal Research Reviews

133

View full text Add to dashboard Cite

Mammalian thioredoxin reductase (TrxR) enzymes are homodimeric flavin proteins sharing a unique yet essential selenocysteine residue at their C-terminus. TrxRs, together with their endogenous substrate thioredoxins, play a crucial role in regulating diverse cellular redox events. A wealth of evidence from both clinic observations and bench studies supports that overactivation/dysfunction of TrxRs has a close link to the onset and development of various diseases, such as cancer and neurodegeneration. Thus, an increasing interest has been attracted to find small molecule modulators of TrxRs during the past years. Herein, we briefly discussed the relevance of targeting TrxRs inhibition for cancer treatment, and presented the small molecule inhibitors of mammalian TrxRs published in the nonpatent literatures from 2011 to 2016. The mechanisms of inhibition by different classes of molecules were summarized, and some inhibitors with promising anticancer activity were further discussed. We expect this work would be a comprehensive reference in the medicinal chemistry, and have a broad audience across multiple disciplines.

show abstract

Section: Thioredoxin Reductase Inhibitorsmentioning

confidence: 99%

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Zhang

et al. 2018

Medicinal Research Reviews

133

View full text Add to dashboard Cite

show abstract

“…Trx1, with a molecular weight of 12 kDa, exists in almost every organism, and exhibits key functions in a number of important biological activities, including redox signaling; it is also a critical factor in tumor development ( 16 ). Specifically, Trx1 can directly inhibit the activity of apoptosis signal-regulated kinase-1 to reduce the rate of tumor cell death and enhance tumor cell growth factor expression, thereby accelerating tumor cell growth ( 17 , 18 ). Trx1 can also induce the synthesis of vascular endothelial growth factor to promote angiogenesis and the extension of tumor blood vessels.…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of post-traumatic stress-related serum factors in children with Wilms' tumors

Zhang

Guo

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Wilms' tumors are one of the most common malignant, solid intra-abdominal tumors observed in children. Although potential tumor markers have been found, inflammatory cytokines interfere with the process of specific protein identification. The present study was undertaken to identify post-traumatic stress-related factors of Wilms' tumors and to verify the accuracy of early-stage tumor-specific serum protein markers. Serum samples were screened for differentially-expressed proteins using surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS). Potential markers were isolated and purified using solid-phase extraction (SPE) and SDS-PAGE. Following enzymatic digestion of the protein samples, the peptide fragments were detected with high performance liquid chromatography-mass spectrometry. The obtained peptide mass fingerprint was searched in the Swiss-Prot protein sequence database via the Mascot search engine. Differentially-expressed proteins were verified using western blot analysis. Differentially-expressed proteins with a mass/charge of 5,816 were screened out using SELDI-TOF-MS, and significant differences between the tumor and control groups, and the trauma and control groups were observed. Target proteins were isolated and purified using SPE and SDS-PAGE. Thioredoxin 1 (Trx1) was found to be differentially expressed. In the serum of children with Wilms' tumors, there was an increase in the level of the post-traumatic stress-related inflammatory factor, Trx1, as compared with the normal control group. Thus, the results of this study indicate that Trx1 presents a potential post-traumatic stress-related factor of Wilms' tumors.

show abstract

“…All novel organotin (IV) derivatives, with the exception of dimethyltin (IV), showed significant cytotoxicity in HT-29 and was suggested to induce cell death via apoptosis (Girasolo et al, 2010). To date, the synthesized diand tri-n-butyltin (IV) carboxylates derivatives against HT-29 colon adenocarcinoma cell line showed a potent anticancer activity via the inhibition of thioredoxin reductase at the micromolar range (Oliveira et al, 2013). These examples demonstrated the organotin (IV) derivatives as apromisingand potent new anticancer drugs that promote a new dimension in anticancer drugs development.…”

Section: Ojbsmentioning

confidence: 99%

CYTOTOXICITY AND MODE OF CELL DEATH INDUCED BY TRIPHENYLTIN (IV) COMPOUNDS <i>IN VITRO</i>

Awang¹,

Aziz

Kamaludin³

et al. 2014

OnLine Journal of Biological Sciences

View full text Add to dashboard Cite

A series of newly synthesized organotin (IV) with N-alkyl-N-phenyldithiocarbamate ligands namely triphenyltin (IV) ethylphenyldithiocarbamate (compound 1) and triphenyltin (IV) butylphenyldithiocarbamate (compound 2) were assessed for their cytotoxic effect against HT-29 human colon adenocarcinoma cells and human CCD-18Co normal colon cells. The cytotoxicity of these organotins in both cells was assessed using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazholium bromide (MTT) assay upon 24 h treatment. Both compounds demonstrated potent cytotoxicity towards HT-29 cells with the IC 50 of 0.18 µM for compound 1 and 0.20 µM for compound 2. Interestingly, compound 1 exhibited lower cytotoxicity towards CCD-18Co with IC 50 of 1.55 µM whereas no IC 50 was detected for compound 2 up to 2 µM treatment. The mode of cell death was determined based on the externalization of phosphatidylserine using flow cytometry. Cells treated with compound 1 and compound 2 were mainly viable and the apoptotic cell death was around 10% which suggests that both compounds induced growth arrest. In conclusion, this study demonstrated that both compounds were selective towards human colorectal cells by giving a strong cytotoxicity to cancer cells and low toxicity towards normal cells. Both compounds were suggested to induce growth arrest in HT-29 cells.

show abstract

Butyltin(IV) Benzoates: Inhibition of Thioredoxin Reductase, Tumor Cell Growth Inhibition, and Interactions with Proteins

Cited by 28 publications

References 59 publications

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update

Screening and identification of post-traumatic stress-related serum factors in children with Wilms' tumors

CYTOTOXICITY AND MODE OF CELL DEATH INDUCED BY TRIPHENYLTIN (IV) COMPOUNDS <i>IN VITRO</i>

Contact Info

Product

Resources

About