Electron-Acceptor Properties of Hypericin and Its Salts: An ESR/ENDOR and Electrochemical Study

Gerson, Fabian; Gescheidt, Georg; Haering, Pascal; Mazur, Yehuda; Freeman, Dalia; Spreitzer, Hubert; Daub, Joerg

doi:10.1021/ja00153a007

Cited by 46 publications

(38 citation statements)

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“…q and d subscripts represent quartet and doublet signals, respectively. Radical dianion species are known for hydroxyquinones of biological importance [20] but, as far as we know, no information regarding the electrochemically mediated generation of such a species and its simultaneous spectroscopic identification, has been reported. In order to validate further the proposal of Eq.…”

Section: Resultsmentioning

confidence: 99%

“…However, in this research, some of the experimental conditions are quite different from those reported previously (Pt, GC vs Hg) and may suggest that the nature of such an electrochemical reaction could depend on the nature of the electrode. It is interesting to note that only reaction 6 can be related to the formation of a stable semiquinone-type radical species (Q-O Å= ), and reports on the stability of these intermediates in the literature are few [20]. In this work, the processes associated with the formation of this radical dianion are discussed by studying a standard compound (2-hydroxy-1,4-naphthoquinone 2, Fig.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

Electrochemical and ESR study on the transformation processes of α-hydroxy-quinones

Frontana¹,

Frontana‐Uribe

González³

2004

Journal of Electroanalytical Chemistry

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Electrochemical and ESR study on the transformation processes of α-hydroxy-quinones

Frontana¹,

Frontana‐Uribe

González³

2004

Journal of Electroanalytical Chemistry

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“…16 The biochemical basis for the observed antitumoral activities of HY in the dark appears to be the relatively low red/ox potential of this molecule, E 1 /VϭϪ1.012 electron volt, measured by electron spin resonance. 23 It may be low enough to enable HY to function as an acceptor from cellular electron transfer reactions and high enough to generate active oxygen species. Indeed, electrochemical studies show that HY has electron accepting as well as electron donating properties and can function as both oxidizing and reducing agents that facilitate the activities in the dark.…”

Section: Discussionmentioning

confidence: 99%

Antimetastatic activity of the photodynamic agent hypericin in the dark

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Lavie²,

Mandel³

et al. 2004

Intl Journal of Cancer

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A unique property of the photodynamic signal transduction inhibitor hypericin (HY) is high functionality in the dark, which has been shown to result in portfolio of anticancer activities both in vitro and in vivo. Here we show that treatment with HY significantly reduces growth rate of metastases in 2 murine models: breast adenocarcinoma (DA3) and squamous cell carcinoma (SQ2 Cancer is currently viewed as a cell cycle disease. Strategies to treat malignancies are thus shifting from toxic chemotherapy to agents that switch-off positive cell replication transducers specifically or to activators of endogenous negative cell cycle regulators (p53, p21 waf1 , Kip and INK families of proteins). 1 The feasibility of the novel approach is exemplified by recent success in achieving clinical remissions by Imatinib Mesylate (Gleevec), a rationally designed catalytic domain inhibitor of Abl, c-Kit and PDGFR tyrosine kinases. [2][3][4] Other agents such as the cyclin-dependent kinase inhibitors, flavopiridol, 7-hydroxystaurosporine (UCN-01) and staurosporine are at different phases of clinical development. 5,6 Additional attractive targets for intracellular signaling inhibition are modulators of the PKC family of isoenzymes. Perihydroxylated perylene quinones constitute a unique class of photoactivated inhibitors of ser/thr kinases. In this group, hypericin (HY) has been reported to inhibit PKC, 7,8 Erk1/2 kinases and also epidermal growth factor receptor tyrosine kinase. 9 -11 Most of these signaltransduction inhibitory activities of hypericin have been attributed to the photodynamic properties of the compound that were achieved when HY was excited by light at wavelengths absorbed by the molecule. 11 However, recent observations suggest that HY, in addition to its light-dependent anticancer activities, 12 possesses potent anticancer activities and ability to inhibit different signal transduction pathways also in the absence of light activation (dark effects). [13][14][15] We recently demonstrated that the newly identified anti-cancer activities of HY in the dark differ from the well-characterized light-induced effects of the compound in kinetics, modes of tumor cell death and their underling mechanisms. 13 Cell death induction by HY with light occurs rapidly. Within hours after light irradiation, cells undergo apoptosis, or if the light dose is high, also necrosis. In the dark, on the other hand, tumor cell exposure to HY is required for at least 48 hr in order to inhibit cell proliferation. At higher HY concentrations (Ͼ 10 M), the compound killed the tumor cells in the dark via mitotic cell death. 16 Mitotic cell death is a process observed in cancer cells following treatment with different chemotherapeutic agents as well as radiotherapy. The phenomenon is characterized by cells accumulation at G 2 /M, uncoupling of apoptosis, increased cell volume and multinucleation leading to cell death. 17 Although the precise mechanisms leading to mitotic cell death are not fully understood, we have recently identified processes by wh...

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“…Validity of this concept with reference to the reduction by zinc is supported by the formation of RA from non-halogenated arenes in the system Zn/OH À /DMSO [27] and from hypercin in the systems Zn/DMF and Zn/DMF/H 2 O [28], as well as by the formation of organozinc compounds from perfluoroarenes under the action of zinc in anhydrous DMF in the presence of some salts [29]. At the same time, the way via protonation of RA as the second stage and the subsequent transformation of an arising cyclohexadienyl radical seems improbable, as the formation of such radical was not recorded spectrophotometrically in the pentafluorophenolate hydrodefluorination effected by hydrated electrons [26].…”

Section: Mechanismmentioning

confidence: 98%

Recent advances in practice and theory of polyfluoroarene hydrodehalogenation

Shteingarts

2007

Journal of Fluorine Chemistry

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Electron-Acceptor Properties of Hypericin and Its Salts: An ESR/ENDOR and Electrochemical Study

Cited by 46 publications

References 0 publications

Electrochemical and ESR study on the transformation processes of α-hydroxy-quinones

Electrochemical and ESR study on the transformation processes of α-hydroxy-quinones

Antimetastatic activity of the photodynamic agent hypericin in the dark

Recent advances in practice and theory of polyfluoroarene hydrodehalogenation

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