Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines

Stromyer, Michael L.; Southerland, Marie R.; Satyal, Uttam; Sikder, Rahmat; Weader, David J.; Baughman, Jessi A.; Youngs, Wiley J.; Abbosh, Philip

doi:10.1016/j.ejmech.2019.111832

Cited by 15 publications

(13 citation statements)

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“…13 . Decrease in mitochondrial membrane potential has been observed in RT112 cells incubated in a new imidazolium IL with a triphenylphosphonium substituent, TPP1 (Stromyer et al 2020 ), see Fig. 14 .…”

Section: Mechanisms Of Action Of Ilsmentioning

confidence: 96%

“… Reduction of fetal weight and malformations have been observed in CD-1 mice treated with [C 4 mim][Cl] (Bailey et al 2008 ). A new imidazolium IL with a triphenylphosphonium substituent (TPP1), applied intravesically to a bladder cancer mouse model induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), has selectively killed cancer cells leaving healthy cells unaffected as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not (Stromyer et al 2020 ), see Fig. 23 .…”

Section: Mechanisms Of Action Of Ilsmentioning

confidence: 99%

“…b Sections of tumor-adjacent normal urothelium area clearly showing that the IL selectively kills cancer cells leaving healthy cells unaffected. Adapted from Stromyer et al ( 2020 ) and reproduced with permission from the publisher

Fig. 24 Typical histopathological views of mouse heart (first row) and of mouse kidney (second and third rows), hematoxylin and eosin–stained sections.…”

Section: Mechanisms Of Action Of Ilsmentioning

confidence: 99%

“…For example, it has been shown that the oral delivery of a choline-based IL prevents the absorption of fat molecules through intestinal tissue in rats (Nurunnabi et al 2019 ). Apart from few very ad hoc “system biology” studies, as the one just mentioned, there are several studies highlighting the specificity of ILs towards cancer cells and their ability to kill those cells, leaving healthy cells almost unaffected (Kumar and Malhotra 2009 ; Malhotra and Kumar 2010 ; Wang et al 2015 ; Stromyer et al 2020 ). In this context, it has been shown, for example, that tri- n -butyl- n -hexadecyl-phosphonium bromide—a phosphonium-based IL with a halogen anion and balanced lengths of C 4 and C 16 alkyl chains—is approximately 100 times more toxic against HeLa cells than several ammonium-based ILs, but it remains inactive against human chronic myelogenous leukemia K562 cells; complementarily, triphenyl-alkyl-phosphonium iodides, with shorter C 1 and C 5 alkyl chains, resulted to be inactive against HeLa cells, but very active against K562 cells (Bachowska et al 2012 ).…”

Section: Introductionmentioning

confidence: 99%

“…In this context, it has been shown, for example, that tri- n -butyl- n -hexadecyl-phosphonium bromide—a phosphonium-based IL with a halogen anion and balanced lengths of C 4 and C 16 alkyl chains—is approximately 100 times more toxic against HeLa cells than several ammonium-based ILs, but it remains inactive against human chronic myelogenous leukemia K562 cells; complementarily, triphenyl-alkyl-phosphonium iodides, with shorter C 1 and C 5 alkyl chains, resulted to be inactive against HeLa cells, but very active against K562 cells (Bachowska et al 2012 ). More recently, (i) a novel betulinic acid–derived IL, i.e., [P 6,6,6,14 ][BA], has shown a specific cytotoxicity against human hepatocellular carcinoma HepG2 and human lung carcinoma A459 tumor cell lines (Silva et al 2019 ), and (ii) a new imidazolium IL with a triphenylphosphonium substituent, applied intravesically to mouse, has selectively killed bladder cancer cells, leaving adjacent healthy cells unaffected (Stromyer et al 2020 ). This selective ability of ILs together with their extreme flexibility in design makes them potential candidates against cancers.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of action of ionic liquids on living cells: the state of the art

2020

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Ionic liquids (ILs) are a relatively new class of organic electrolytes composed of an organic cation and either an organic or inorganic anion, whose melting temperature falls around room-temperature. In the last 20 years, the toxicity of ILs towards cells and micro-organisms has been heavily investigated with the main aim to assess the risks associated with their potential use in (industrial) applications, and to develop strategies to design greener ILs. Toxicity, however, is synonym with affinity, and this has stimulated, in turn, a series of biophysical and chemical-physical investigations as well as few biochemical studies focused on the mechanisms of action (MoAs) of ILs, key step in the development of applications in bio-nanomedicine and bio-nanotechnology. This review has the intent to present an overview of the state of the art of the MoAs of ILs, which have been the focus of a limited number of studies but still sufficient enough to provide a first glimpse on the subject. The overall picture that emerges is quite intriguing and shows that ILs interact with cells in a variety of different mechanisms, including alteration of lipid distribution and cell membrane viscoelasticity, disruption of cell and nuclear membranes, mitochondrial permeabilization and dysfunction, generation of reactive oxygen species, chloroplast damage (in plants), alteration of transmembrane and cytoplasmatic proteins/enzyme functions, alteration of signaling pathways, and DNA fragmentation. Together with our earlier review work on the biophysics and chemical-physics of IL-cell membrane interactions (Biophys. Rev. 9:309, 2017), we hope that the present review, focused instead on the biochemical aspects, will stimulate a series of new investigations and discoveries in the still new and interdisciplinary field of “ILs, biomolecules, and cells.”

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Section: Mechanisms Of Action Of Ilsmentioning

confidence: 96%

Section: Mechanisms Of Action Of Ilsmentioning

confidence: 99%

Fig. 24 Typical histopathological views of mouse heart (first row) and of mouse kidney (second and third rows), hematoxylin and eosin–stained sections.…”

Section: Mechanisms Of Action Of Ilsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mechanisms of action of ionic liquids on living cells: the state of the art

2020

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An Imidazolium‐Based Lipid Analogue as a Gene Transfer Agent

Bornemann

Herzog

Kudruk

et al. 2020

Chemistry A European J

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A dicationic imidazolium salt is described and investigated towards its application for gene transfer. The polar head group and the long alkyl chains in the backbone contribute to a lipid‐like behavior, while an alkyl ammonium group provides the ability for crucial electrostatic interaction for the transfection process. Detailed biophysical studies regarding its impact on biological membrane models and the propensity of vesicle fusion are presented. Fluorescence spectroscopy, atomic force microscopy and confocal fluorescence microscopy show that the imidazolium salt leads to negligible changes in lipid packing, while displaying distinct vesicle fusion properties. Cell culture experiments reveal that mixed liposomes containing the novel imidazolium salt can serve as plasmid DNA delivery vehicles. In contrast, a structurally similar imidazolium salt without a second positive charge showed no ability to support DNA transfection into cultured cells. Thus, we introduce a novel and variable structural motif for cationic lipids, expanding the field of lipofection agents.

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2‐Aryl Imidazolium Salts as Potential Bladder Cancer Chemotherapeutic Candidates

Hobbs,

Chen,

Youngs

et al. 2023

ChemistrySelect

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As potential intravesical exfoliants for the treatment of bladder cancer, four new imdiazolium salts have been prepared. These compounds are modified on the nitrogen positions of the 4,5‐diphenyl‐1H‐imidazole or benzimidazole rings with naphthalen‐2‐ylmethyl groups, and the 2 positions on the azolium cations are occupied by arene rings. The 4,5‐diphenyl‐1H‐imidazole and benzimidazole precursors are produced from 1,2‐phenylenediamine and benzil respectively, and the imidazolium cations are generated from sequential alkylation of the nitrogen positions using 2‐bromomethyl naphthalene. The four imidazolium salts were screened for their chemotherapuetic activity using the NCI‐60 Human Tumour Cell Line Screen, and we observed that the cytotoxicity was more dependent on the identity of the imidazolium group (benzimidazolium versus diphenylimidazolium) rather than on the 2‐aryl position structure.

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Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines

Cited by 15 publications

References 56 publications

Mechanisms of action of ionic liquids on living cells: the state of the art

Mechanisms of action of ionic liquids on living cells: the state of the art

An Imidazolium‐Based Lipid Analogue as a Gene Transfer Agent

2‐Aryl Imidazolium Salts as Potential Bladder Cancer Chemotherapeutic Candidates

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