Photosensitizing Merocyanine Dyes Based on Selenobarbituric Acid

Günther, Wolfgang; Searle, Roger; Sieber, Fritz

doi:10.1080/10426509208045864

Cited by 16 publications

(21 citation statements)

References 7 publications

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“…The spectral characteristics (peak absorption wavelength, peak fluorescence emission wavelength) of the primary chromophore photoproduct were indeed indistinguishable from the spectral characteristics of dye MC47 (Fig. 1), the authentic barbituric acid analog of MC54 (1,2). The higher fluorescence quantum yield of the primary chromophore photoproduct was also consistent with a replacement of the original selone dye by its oxone analog (1).…”

Section: Resultsmentioning

confidence: 79%

“…To screen photosensitizing dyes for their capacity to generate cytotoxic photoproducts, MC540, 13 structural analogues selected from Günther’s (1) series of second‐generation merocyanine dyes, and one selenooxonol dye (Fig. 1) were dissolved in serum‐supplemented alpha‐medium and photobleached by exposure to cool white fluorescent light.…”

Section: Resultsmentioning

confidence: 99%

“…1), the authentic barbituric acid analog of MC54 (1,2). The higher fluorescence quantum yield of the primary chromophore photoproduct was also consistent with a replacement of the original selone dye by its oxone analog (1).…”

Section: Resultsmentioning

confidence: 99%

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Photochemically Generated Elemental Selenium Forms Conjugates with Serum Proteins That Are Preferentially Cytotoxic to Leukemia and Selected Solid Tumor Cells

Daziano

Günther

Krieg³

et al. 2012

Photochem & Photobiology

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The objective of this study was to determine if and how photoproducts contribute to the anti-tumor effect of merocyanine-mediated PDT. A panel of barbituric, thiobarbituric and selenobarbituric acid analogues of Merocyanine 540 was photobleached, and the resulting photoproducts were characterized by absorption, fluorescence emission, mass, energy dispersive X-ray, and X-ray photoelectron spectroscopy, and tested for cytotoxic activity against tumor cell lines and freshly explanted bone marrow cells. While all dyes were readily photobleached, only photoproducts of selone dyes showed cytotoxic activity. One-hour incubations with micromolar concentrations of selone-derived photoproducts were sufficient to reduce leukemia/lymphoma cells ≥10,000 fold while preserving virtually all normal CD34-positive bone marrow cells. Of 6 multi-drug resistant tumor cell lines tested, 5 were as sensitive or more sensitive to photoproducts than the corresponding wild-type lines. Physicochemical characterizations of the cytotoxic activity indicated that it consisted of conjugates of subnano particles of elemental selenium and (lipo)proteins. The discovery of cytotoxic Se-protein conjugates provides a rare example of photoproducts contributing substantially to the anti-tumor effect of PDT and challenges the long-held view that Se in oxidation state zero is biologically inert. Agents modeled after our Se-protein conjugates may prove useful for the treatment of leukemia.

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Section: Resultsmentioning

confidence: 79%

Section: Resultsmentioning

confidence: 99%

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Photochemically Generated Elemental Selenium Forms Conjugates with Serum Proteins That Are Preferentially Cytotoxic to Leukemia and Selected Solid Tumor Cells

Daziano

Günther

Krieg³

et al. 2012

Photochem & Photobiology

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“…Structural analogues of MC540 ( Fig. 1) were synthesized as described by Giinther et al (20). Selenium-containing analogues were >95% pure; all other merocyanine dyes were >98% pure.…”

Section: Methodsmentioning

confidence: 99%

Inactivation of Photosensitizing Merocyanine Dyes by Plasma, Serum and Serum Components

Andérson

Günther²,

Searle³

et al. 1996

Photochem & Photobiology

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Merocyanine dyes with an oxygen in the electron donor heterocycle were rapidly degraded by plasma, serum and serum components. Replacement of the oxygen by a sulfur or selenium atom rendered the dyes refractory to degradation. The degradation of labile merocyanine dyes was temperature dependent and oxygen independent. The plasma component that was responsible for the degradation of merocyanine dyes was sensitive to heat and detergent, suggesting an enzymatic process. The identification of the structural requirements for sensitivity/resistance to degradation provides the experimenter with a simple means to manipulate the stability of merocyanines in high serum or plasma environments and may expand the clinical utility of merocyanine photosensitizers beyond their traditional role in the extracorporeal purging of bone marrow grafts.

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“…Dyes: Merocyanine dyes were synthesized as described by Günther et al 1 The bis-(1,3-dibutyl selenobarbituric acid) trimethine oxonol dye was synthesized as described by Krieg et al 3 All selone dyes were ≥95% pure. All thiobarbituric and barbituric acid analogues were ≥98% pure.…”

Section: Methodsmentioning

confidence: 99%

Elemental Selenium Generated by the Photobleaching of Seleno-Merocyanine Photosensitizers Forms Conjugates with Serum Macro-Molecules That are Toxic to Tumor Cells

Sieber

Daziano

Günther

et al. 2005

Phosphorus, Sulfur, and Silicon and the Related Elements

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Elemental selenium generated by the photobleaching of selenomerocyanine dyes forms conjugates with serum albumin and serum lipoproteins that are toxic to leukemia and selected solid tumor cells but well tolerated by normal CD34-positive hematopoietic stem and progenitor cells. Serum albumin and lipoproteins act as Trojan horses that deliver the cytotoxic entity (elemental selenium) to tumor cells as part of a physiological process. They exploit the fact that many tumors have an increased demand for albumin and/or low-density lipoprotein. Se(0)-protein conjugates are more toxic than selenium dioxide, sodium selenite, selenomethionine, or selenocystine. They are only minimally affected by drug resistance mechanism, and they potentiate the cytotoxic effect of ionizing radiation and several standard chemotherapeutic agents. The cytotoxic mechanism of Se(0)-protein conjugates is not yet fully understood. Currently available data are consistent with the notion that Se(0)-protein conjugates act as air oxidation catalysts that cause a rapid depletion of intracellular glutathione and induce apoptosis. Drugs modeled after our Se(0)-protein conjugates may prove useful for the local and/or systemic therapy of cancer.

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Photosensitizing Merocyanine Dyes Based on Selenobarbituric Acid

Cited by 16 publications

References 7 publications

Photochemically Generated Elemental Selenium Forms Conjugates with Serum Proteins That Are Preferentially Cytotoxic to Leukemia and Selected Solid Tumor Cells

Photochemically Generated Elemental Selenium Forms Conjugates with Serum Proteins That Are Preferentially Cytotoxic to Leukemia and Selected Solid Tumor Cells

Inactivation of Photosensitizing Merocyanine Dyes by Plasma, Serum and Serum Components

Elemental Selenium Generated by the Photobleaching of Seleno-Merocyanine Photosensitizers Forms Conjugates with Serum Macro-Molecules That are Toxic to Tumor Cells

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