From Catalysts to Bioactive Organometallics: Do Grubbs Catalysts Trigger Biological Effects?

Oehninger, Luciano; Alborzinia, Hamed; Ludewig, Stephanie; Baumann, Knut; Wölfl, Stefan; Ott, Ingo

doi:10.1002/cmdc.201100308

Cited by 38 publications

(42 citation statements)

References 32 publications

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“…[12][13][14][15] This type of complex showed among other effects a strong and selective inhibition of the enzyme thioredoxin reductase (TrxR), induction of apoptosis, or depolarization of the mitochondrial membrane. [14,[16][17][18][19] Besides gold and silver, other metals including platinum, [20][21][22][23][24] palladium, [25,26] ruthenium, [27][28][29] or rhodium [30,31] have also been used as centers of bioactive NHC complexes.…”

Section: Introductionmentioning

confidence: 99%

A Chemical–Biological Evaluation of Rhodium(I) N‐Heterocyclic Carbene Complexes as Prospective Anticancer Drugs

Oehninger

Küster

Schmidt

et al. 2013

Chemistry A European J

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Rhodium(I) complexes bearing N-heterocyclic carbene (NHC) ligands have been widely used in catalytic chemistry, but there are very few reports of biological properties of these organometallics. A series of Rh(I)-NHC derivatives with 1,5-cyclooctadiene and CO as secondary ligands were synthesized, characterized, and biologically investigated as prospective antitumor drug candidates. Pronounced antiproliferative effects were noted for all complexes, along with moderate inhibitory activity of thioredoxin reductase (TrxR) and efficient binding to biomolecules (DNA, albumin). Biodistribution studies showed that the presence of albumin lowered the cellular uptake and confirmed the transport of rhodium into the nuclei. Changes in the mitochondrial membrane potential (MMP) were observed as well as DNA fragmentation in wild-type and daunorubicin- or vincristine-resistant Nalm-6 leukemia cells. Overall, these studies indicated that Rh(I)-NHC fragments could be used as partial structures of new antitumor agents, in particular in those drugs designed to address resistant malignant tissues.

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Section: Introductionmentioning

confidence: 99%

A Chemical–Biological Evaluation of Rhodium(I) N‐Heterocyclic Carbene Complexes as Prospective Anticancer Drugs

Oehninger

Küster

Schmidt

et al. 2013

Chemistry A European J

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“…A total of 17 compounds selected by visual postprocessing of the hit lists were subsequently studied for TrxR inhibition (see Supporting Information), one of which was the tin(IV) organometallic compound 2. [13] The known inhibitory activity of organometallic compounds [23,24] motivated the selection of compound 2 for experimental validation, and it was shown to be one of the most active hits from the screening. The organometallic character of this compound suggests a binding mode similar to the platinum(II) terpyridine (TPT) compound shown in Figure 2 B.…”

Section: Resultsmentioning

confidence: 99%

“…[23,24] Tri-nbutyltin(IV) chloride and di-n-butyltin(IV) oxide were included in the experiments as references. [23,24] Tri-nbutyltin(IV) chloride and di-n-butyltin(IV) oxide were included in the experiments as references.…”

Section: Inhibition Of Trxr and Antiproliferative Effectsmentioning

confidence: 99%

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

et al. 2012

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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.

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“…To investigate cellular uptake and the cytotoxicity of Ru-BPPBIhx-SQ, two well-known human cancer cell lines were used, HT-29 colorectal and MCF-7 breast lines, frequently employed to screen drug compounds and, in particular used to test several Ru complexes (Oehninger et al, 2011;Reddy et al, 2012;Schatzschneider et al, 2008). (Neugebauer et al, 2008) (Puckett and Barton, 2007) (phen = 1,l0-phenanthroline; dppz = dipyrido[3,2-a:2 ,3 -c]phenazine).…”

Section: In Vitro Activity: Cellular Uptakementioning

confidence: 99%

Ruthenium polypyridyl squalene derivative: A novel self-assembling lipophilic probe for cellular imaging

Dosio¹,

Stella²,

Ferrero³

et al. 2013

International Journal of Pharmaceutics

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Transition metal complexes provide a promising avenue for designing new therapeutic and diagnostic agents. In particular, ruthenium(II) polypyridyl complexes are useful for studying cellular uptake, due to their easy synthesis and unique photophysical properties. Dyes are frequently combined with material substrates to modulate their properties, enhance stability, reduce toxicity, and improve delivery. A novel Ru polypyridyl complex linked to a derivative of the natural lipid squalene (Ru-BIPPBI-hx-SQ) is described. Using the solvent displacement method, Ru-BIPPBI-hx-SQ easily self-assembles into nanosized aggregates in aqueous solution, as characterized by dynamic light scattering. The nanoassemblies exhibit long-lived and intense luminescence.Preliminary biological assessment showed them to be non-toxic; they are efficiently and rapidly transported across the cell membrane without requiring its permeabilization. Ru-labeled nanoassemblies are likely to be significant cellular-imaging tools, probing cellular events at very low concentrations. Moreover co-nanoassembly, with drug-derivatives based on squalenoylation technology, including gemcitabine and paclitaxel, has given interesting preliminary results.

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From Catalysts to Bioactive Organometallics: Do Grubbs Catalysts Trigger Biological Effects?

Cited by 38 publications

References 32 publications

A Chemical–Biological Evaluation of Rhodium(I) N‐Heterocyclic Carbene Complexes as Prospective Anticancer Drugs

A Chemical–Biological Evaluation of Rhodium(I) N‐Heterocyclic Carbene Complexes as Prospective Anticancer Drugs

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

Ruthenium polypyridyl squalene derivative: A novel self-assembling lipophilic probe for cellular imaging

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