The chemistry of the- NCS group

Drobnica, L; Kristián, Pavol; Augustín, Jozef

doi:10.1002/9780470771532.ch6

Cited by 120 publications

(113 citation statements)

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“…Isothiocyanate-mediated disruption of cancer progression is achieved by a variety of mechanisms including modulation of cell growth (5), inhibition of angiogenesis (6), suppression of metastasis (7), and induction of apoptosis (8, 9). Isothiocyanates can also modulate inflammatory pathways via inhibition of the transcription factor nuclear factor B (10).The electrophilic carbon residue in the isothiocyanate moiety (-NACAS) is capable of reacting with biological nucleophiles such as cysteine in proteins and the tripeptide glutathione (11,12). Binding of isothiocyanates to Kelch-like ECH-associated protein 1 (Keap1) (13), transient receptor potential channels (14), MEKK1 protein kinase (15), and tubulin (16) has been demonstrated to occur via covalent modification of cysteine.…”

mentioning

confidence: 99%

“…The electrophilic carbon residue in the isothiocyanate moiety (-NACAS) is capable of reacting with biological nucleophiles such as cysteine in proteins and the tripeptide glutathione (11,12). Binding of isothiocyanates to Kelch-like ECH-associated protein 1 (Keap1) (13), transient receptor potential channels (14), MEKK1 protein kinase (15), and tubulin (16) has been demonstrated to occur via covalent modification of cysteine.…”

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confidence: 99%

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Direct Modification of the Proinflammatory Cytokine Macrophage Migration Inhibitory Factor by Dietary Isothiocyanates

Brown

Blaikie

Smith

et al. 2009

Journal of Biological Chemistry

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Isothiocyanates are a class of phytochemicals with widely reported anti-cancer and anti-inflammatory activity. However, knowledge of their activity at a molecular level is limited. The objective of this study was to identify biological targets of phenethyl isothiocyanate (PEITC) using an affinity purification approach. An analogue of PEITC was synthesized to enable conjugation to a solid-phase resin. The pleiotropic cytokine macrophage migration inhibitory factor (MIF) was the major protein captured from cell lysates. Site-directed mutagenesis and mass spectrometry showed that PEITC covalently modified the N-terminal proline residue of MIF. This resulted in complete loss of catalytic tautomerase activity and disruption of protein conformation, as determined by impaired recognition by a monoclonal antibody directed to the region that receptors and interacting proteins bind to MIF. The conformational change was supported by in silico modeling. Monoclonal antibody binding to plasma MIF was disrupted in humans consuming watercress, a major dietary source of PEITC. The isothiocyanates have significant potential for development as MIF inhibitors, and this activity may contribute to the biological properties of these phytochemicals.Isothiocyanates are a class of phytochemicals with recognized anti-cancer activity. They can act in a chemopreventive capacity via inhibition of carcinogen-activating phase I enzymes (1) and induction of phase II detoxification enzymes (2). Isothiocyanates are also active in the post-initiation phase of tumorigenesis and are, therefore, proposed to have chemotherapeutic potential (3, 4). Isothiocyanate-mediated disruption of cancer progression is achieved by a variety of mechanisms including modulation of cell growth (5), inhibition of angiogenesis (6), suppression of metastasis (7), and induction of apoptosis (8, 9). Isothiocyanates can also modulate inflammatory pathways via inhibition of the transcription factor nuclear factor B (10).The electrophilic carbon residue in the isothiocyanate moiety (-NACAS) is capable of reacting with biological nucleophiles such as cysteine in proteins and the tripeptide glutathione (11,12). Binding of isothiocyanates to Kelch-like ECH-associated protein 1 (Keap1) (13), transient receptor potential channels (14), MEKK1 protein kinase (15), and tubulin (16) has been demonstrated to occur via covalent modification of cysteine. Reaction with amines to form stable thiourea derivatives can also occur. However, this is generally considered to be a less favorable reaction at physiological pH (11).To elucidate the major cellular targets of biologically active isothiocyanates, we have utilized an affinity-based target identification approach. An amine linker was added to phenethyl isothiocyanate (PEITC) 3 without compromising cytotoxicity, and the molecule was immobilized to a solid phase resin. The pleiotropic cytokine macrophage migration inhibitory factor (MIF) was identified as a major biological target of PEITC. Using mass spectrometry and site-directed mutagene...

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confidence: 99%

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confidence: 99%

Direct Modification of the Proinflammatory Cytokine Macrophage Migration Inhibitory Factor by Dietary Isothiocyanates

Brown

Blaikie

Smith

et al. 2009

Journal of Biological Chemistry

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“…phenethylisothiocyanate is approximately 24-time less reactive than AcITC(ref. 13 ). The kinetic parameters for the reactions of 9-isothiocyana-…”

Section: Resultsmentioning

confidence: 99%

Involvement of Glutathione in the Cytotoxicity of 9-Isothiocyanatoacridine

Paulíková¹,

Bajdichova²,

Sovcikova³

et al. 2005

BIOMED PAP

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Isothiocyanates (ITCs) are phytochemicals with promising cancer-preventive potential. To elucidate the mechanism of cytotoxicity of ITCs, their accumulation by cells and the role of intracellular glutathione, fluorescent 9-isothiocyanatoacridine (AcITC) was synthesized. The kinetic parameters for the reactions of AcITC with thiols were estimated and the influence of AcITC on human chronic myeloid leukemia cell line (K562) in regard to intracellular glutathione was studied. Cytotoxicity was evaluated by MTT assay, IC 50 =29.2 ± 2.5 µM (48 h incubation). This acridine derivative was able to induce apoptosis of cells (morphological changes of cells and DNA fragmentation were observed) at least within certain dose that only decreased the level of intracellular glutathione, excessive doses (completely depleted intracellular pool of glutathione) induced necrosis rather than apoptosis. Our results indicated that apoptosis of leukemia cells induced by ITC is possible only if intracellular glutathione is not entirely depleted.

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“…ITCs react effectively with free amino acids, N-terminal amino acids bound in peptide chains, disulfide bonds etc. (Drobnica et al 1977). The reactions can proceed during storage, cooking or food processing as well as in the human digestive system.…”

Section: Introductionmentioning

confidence: 99%

“…The reactions can proceed during storage, cooking or food processing as well as in the human digestive system. The kinetics and mechanism of the formation of the N-substituted thiocarbamoyl amino acids and their cyclic forms, 3,5-disubstituted 2-thiohydantoins, were thoroughly described by Drobnica et al (1977) and Cejpek et al (2000a, b).…”

Section: Introductionmentioning

confidence: 99%

Advances in Chemistry of Isothiocyanate-derived Colourants

Cejpek¹,

Velı́šek²

2009

Czech J. Food Sci.

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This study is focused on the reactions of isothiocyanates (ITCs) in the presence of amino compounds leading to coloured structures via substituted 2-thiohydantoins. A series of complementary experiments has been done and appropriate reaction conditions and structural prerequisites have been defined. Low-molecular colourants isolated and characterised from the model systems can be sorted into three groups. Yellow to red diastereomeric dehydrodimers of 2-thiohydantoin derivatives that contain an acidic methylene group are formed in mixtures consisted of ITCs and amino acids with α-methylene group in mild acidic to mild alkaline systems. The condensation products of the 2-thiohydantoins with reactive aromatic or heterocyclic carbaldehydes from the Maillard reaction, essential oils etc. comprise a heterogeneous group of mostly yellow colourants. Blue compounds of two types are structurally more complicated structures that arise from N-substituted amino acids and ITCs in alkaline media.

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The chemistry of the- NCS group

Cited by 120 publications

References 1 publication

Direct Modification of the Proinflammatory Cytokine Macrophage Migration Inhibitory Factor by Dietary Isothiocyanates

Direct Modification of the Proinflammatory Cytokine Macrophage Migration Inhibitory Factor by Dietary Isothiocyanates

Involvement of Glutathione in the Cytotoxicity of 9-Isothiocyanatoacridine

Advances in Chemistry of Isothiocyanate-derived Colourants

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