Development of Benzofurazan−bearing Fluorescence Labeling Reagents for Separation and Detection in High−performance Liquid Chromatography

Toyo’oka, Toshimasa

doi:10.15583/jpchrom.2012.001

Cited by 13 publications

(11 citation statements)

References 69 publications

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“…Nitro-benzoxadiazole (NBD), also referred to as nitro-benzofurazan, and its derivatives can interact with functional groups in proteins and have therefore been employed in developing molecular probes 22 and fluorescent dyes for cell imaging 23 24 . Furthermore, NBD compounds have been used to target proteins of therapeutic significance, such as glutathione S-transferase (GSH) 25 , c-Myc oncogene 26 , and HIV integrase 27 .…”

mentioning

confidence: 99%

Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1

Sakanyan¹,

Hulin²,

Sousa³

et al. 2016

Sci Rep

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Activation of cell signaling by reactive chemicals and pollutants is an important issue for human health. It has been shown that lipophilic nitro-benzoxadiazole (NBD) compounds rapidly move across the plasma membrane and enhance Epidermal Growth Factor Receptor (EGFR) tyrosine phosphorylation in cancer cells. Unlike ligand-dependent activation, the mechanism of this induction relies on the generation of hydrogen peroxide, which is involved in the activation of the catalytic site of the receptor and the inactivation of protein tyrosine phosphatase PTP-1B. Production of H2O2 during redox transformation of NBD compounds is associated with the transition of a monomeric form of Cu/Zn superoxide dismutase 1 (SOD1) to stable dimers. The highly stable and functionally active SOD1 dimer, in the absence of adequate activities in downstream reactions, promotes the disproportionate production and accumulation of intracellular hydrogen peroxide shortly after exposure to NBD compounds. The intrinsic fluorescence of small compounds was used to demonstrate their binding to SOD1. Our data indicate that H2O2 and concomitantly generated electrophilic intermediates behave as independent entities, but all contribute to the biological reactivity of NBD compounds. This study opens a promising path to identify new biomarkers of oxidative/electrophilic stress in the progression of cancer and other diseases.

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mentioning

confidence: 99%

Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1

Sakanyan¹,

Hulin²,

Sousa³

et al. 2016

Sci Rep

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“…Similar molecules bearing this scaffold were next detected in the French National Chemical Library by virtual screening. A tworing structure of NBD emits intrinsic fluorescence, and this property was employed in the development of molecular probes and fluorescent dyes for cell imaging [20]. However, the biologically relevant consequences of this important class of chemicals were still obscure at the beginning of our investigations.…”

Section: Epidermal Growth Factor Receptor As a Paradigm For Screeningmentioning

confidence: 99%

“…The benzoxadiazole (benzofurazan) scaffold is a popular template for the creation of imaging probes in living cells [20,32] and the development of drugs [31,41]. It has been suggested that the anticancer effects of NBD compounds are related to the action of hydrogen peroxide generated during the redox cycling in cancer cells [42].…”

Section: Electrophilic and Oxidative Stress Are Mutually And Tightly mentioning

confidence: 99%

Reactive Chemicals and Electrophilic Stress in Cancer

Sakanyan¹

2018

Preprint

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Exogenous reactive chemicals can impair cellular homeostasis and are often associated with the progression of cancer. Significant progress has been achieved by studying the interactions of chemicals that possess various electron-withdrawing groups and the elucidation of the protective responses of cells to chemical interventions. However, the formation of electrophilic species inside the cell remains largely unclear. Derivatives of nitro-benzoxadiazole (also referred as nitrobenzofurazan) are potent producers of hydrogen peroxide and have been used as a model to elucidate the generation of reactive species in cancer cells. This survey highlights the pivotal role of Cu/Zn superoxide dismutase 1 (SOD1) in the rapid generation of reactive oxygen and electrophilic species in cells exposed to cell-permeable chemicals. Lipophilic electrophiles bind to SOD1 and induce stable and functionally active dimers, which produce excess hydrogen peroxide leading to aberrant cell signalling. Moreover, reactive oxygen species and reactive electrophilic species, simultaneously generated by redox reactions, behave as independent entities that attack a variety of proteins. The identification of proteins susceptible to electrophiles at early steps of oxidative and electrophilic stress is a promising way to offer rational strategies for dealing with stress-related malignant tumors.

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“…The reagents described in the previous sections are useful for the sensitive and specific analysis of amines and carboxylic acids by fluorometry [58][59][60][61][62][63] and MS. [7][8][9][10][11][12][13] However, the determination of each enantiomer of chiral molecules is essentially impossible because there is no chiral recognition moiety in the reagent structures. Therefore, chiral-derivatization reagents for the separation and detection of a pair of enantiomers were also developed in our laboratories (Fig.…”

Section: Reagents For Chiral Amines and Carboxylic Acidsmentioning

confidence: 99%

Derivatization-based High-throughput Bioanalysis by LC-MS

Toyo’oka

2017

ANAL. SCI.

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Liquid chromatography coupled with mass spectrometry (LC-MS) is one of the most prominent analytical techniques due to its inherent selectivity and sensitivity. LC-MS is currently the first choice for high-throughput bioanalysis due to the advancements in MS instruments and the analytical software. Based on this situation, we are developing various types of derivatization reagents, including chiral reagents for MS and/or MS/MS detection. These developed reagents are adopted for the detection of biomarker candidates related to diseases. The biomarker candidates include not only achiral molecules, but also chiral ones. Although determining the already-identified chiral molecules is relative easy, it is very difficult to identify and/or determine unknown enantiomer(s) in real samples. To solve this difficulty, we proposed a new strategy to identify unknown enantiomeric biomarkers related to diseases. This review paper deals with the development of derivatization reagents for amines and carboxylic acids in LC-MS analysis and their application to bioanalysis.

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Development of Benzofurazan−bearing Fluorescence Labeling Reagents for Separation and Detection in High−performance Liquid Chromatography

Cited by 13 publications

References 69 publications

Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1

Activation of EGFR by small compounds through coupling the generation of hydrogen peroxide to stable dimerization of Cu/Zn SOD1

Reactive Chemicals and Electrophilic Stress in Cancer

Derivatization-based High-throughput Bioanalysis by LC-MS

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