Journal ArticleDOI
Butyltin(IV) benzoates: inhibition of thioredoxin reductase, tumor cell growth inhibition, and interactions with proteins.
Kely Navakoski de Oliveira,Vincent Andermark,Susanne von Grafenstein,Liliane A. Onambele,Gregor Dahl,Riccardo Rubbiani,Gerhard Wolber,Chiara Gabbiani,Luigi Messori,Aram Prokop,Ingo Ott +10 more
TLDR
All synthesized compounds were able to inhibit TrxR selectively within the micromolar range and showed potent antitumor activity against HT‐29 and MCF‐7 cancer cell lines, and tin(IV) organometallics were found to strongly induce apoptosis in the BJAB lymphoma cell line.Abstract:
Thioredoxin reductase (TrxR) is overexpressed in cancer cells and is therefore a putative cancer target. Inhibition of this enzyme is considered an important strategy for the development of new chemotherapeutic agents with a specific mechanism of action. Organotin compounds have been described as experimental antitumor agents, yet their mechanism of action remains largely unknown. Based on the outcome of a virtual screening study, various di- and tri-n-butyltin(IV) carboxylates were synthesized, and their biological properties were evaluated. All synthesized compounds were able to inhibit TrxR selectively within the micromolar range and showed potent antitumor activity against HT-29 and MCF-7 cancer cell lines. Moreover, tin(IV) organometallics were found to strongly induce apoptosis in the BJAB lymphoma cell line. Mass spectrometry and atomic absorption spectroscopy experiments revealed metal binding to proteins, and efficient cellular uptake was observed using a di-n-butyltin(IV) complex as an example.read more
Citations
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Next-Generation Metal Anticancer Complexes: Multitargeting via Redox Modulation
TL;DR: The possibility that targeting the redox balance in cancer cells may also be a highly effective strategy, especially because it is a multiple-site approach and offers selectivity over normal cells.
Journal ArticleDOI
Organotin polymers as anticancer and antiviral agents
TL;DR: Organotin polymers are easily synthesized employing interfacial polymerization systems involving the reaction of difunctional Lewis bases and organotin halides and have been shown to exhibit a wide range of biological activities including the inhibition of a wide variety of cancer cell lines including cell lines associated with ovarian, colon, lung, prostrate, pancreatic and breast cancer as mentioned in this paper.
Journal ArticleDOI
Small molecule inhibitors of mammalian thioredoxin reductase as potential anticancer agents: An update.
TL;DR: The relevance of targeting TrxRs inhibition for cancer treatment is discussed, and the small molecule inhibitors of mammalian TrxR published in the nonpatent literatures from 2011 to 2016 are presented.
Journal ArticleDOI
Significance of the mitochondrial thioredoxin reductase in cancer cells: An update on role, targets and inhibitors.
TL;DR: The selective inhibition of TrxR2 could be utilized to induce cancer cell apoptosis, a key role in redox signaling pathways, focusing especially on the impact on mitochondrial pathophysiology.
Journal ArticleDOI
Anti-proliferative and antitumor activity of organotin(IV) compounds. An overview of the last decade and future perspectives.
TL;DR: Much work has been carried out on organotin(IV) derivatives with O-donor ligands, however significant fewer reports are found on organotins( IV) with oximes as ligands.
References
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Journal ArticleDOI
The Protein Data Bank
Helen M. Berman,John D. Westbrook,Zukang Feng,Gary L. Gilliland,Talapady N. Bhat,Helge Weissig,Ilya N. Shindyalov,Philip E. Bourne +7 more
TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Journal ArticleDOI
A computational procedure for determining energetically favorable binding sites on biologically important macromolecules.
TL;DR: The interaction of a probe group with a protein of known structure is computed at sample positions throughout and around the macromolecule, giving an array of energy values.
Journal ArticleDOI
LigandScout: 3-D pharmacophores derived from protein-bound ligands and their use as virtual screening filters.
Gerhard Wolber,Thierry Langer +1 more
TL;DR: Three-dimensional pharmacophore models are constructed, which are sufficiently selective to identify the described binding mode and are thus a useful tool for in-silico screening of large compound databases.
Journal ArticleDOI
Organometallic Anticancer Compounds
TL;DR: The quest for alternative drugs to the well-known cisplatin and its derivatives, which are still used in more than 50% of the treatment regimes for patients suffering from cancer, is highly needed, and organometallic compounds have recently been found to be promising anticancer drug candidates.
Journal ArticleDOI
On the medicinal chemistry of gold complexes as anticancer drugs
TL;DR: The spectrum of gold complexes described as antiproliferative compounds comprises a broad variety of different species including many phosphine complexes as well as gold in different oxidation states.