The Experts below are selected from a list of 66 Experts worldwide ranked by ideXlab platform
Hans Jornvall - One of the best experts on this subject based on the ideXlab platform.
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a yellow component associated with human transthyretin has properties like a Pterin Derivative 7 8 dihydroPterin 6 carboxaldehyde
FEBS Letters, 1995Co-Authors: Ulf Ernstrom, Tom Pettersson, Hans JornvallAbstract:Abstract Transthyretin (TTR) in plasma is associated with yellow compounds. Their properties differ, and in the chicken protein a major yellow compound has recently been identified as a carotenoid, lutein, also called xanthophyll. We now show that the major yellow component extracted from human TTR has properties like a Pterin Derivative, 7,8-dihydroPterin-6-carboxyaldehyde (2-amino-4-hydroxy-6-formyl-7,8-dihydropteridine). The human TTR Derivative has chromatographic and spectral properties identical to a yellow photochemical degradation product of bioPterin and a spectrum like that of the Pterin aldehyde.
Kazuhiko Fukuda - One of the best experts on this subject based on the ideXlab platform.
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the radical scavenger edaravone 3 methyl 1 phenyl 2 pyrazolin 5 one reacts with a Pterin Derivative and produces a cytotoxic substance that induces intracellular reactive oxygen species generation and cell death
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Toshiyuki Arai, Mitsuru Nonogawa, Keisuke Makino, Nobuyuki Endo, Hiroko Mori, Takashi Miyoshi, Kouhei Yamashita, Masataka Sasada, Masahiro Kakuyama, Kazuhiko FukudaAbstract:Cytotoxic effects of the combined use of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger and an approved medicine for acute brain infarction in Japan, with a Pterin Derivative, were examined in vitro. When pancreatic cancer cell line Panc-1 cells were incubated with 50 to 400 μM of a Pterin Derivative, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (DFP), and the equivalent dose of edaravone, reactive oxygen species (ROS), were generated, and cell death was induced. ROS generation and the loss of mitochondrial membrane potential (MMP) preceding cell death were simultaneously monitored using time-lapse microscopy with an ROS-sensitive dye and a probe to monitor MMP, respectively. Cell death was also estimated quantitatively by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. ROS generation and cell death were prominent when more than 100 μM of each agent was used in combination, whereas the sole use of each agent did not show any effects even at the highest dose, 400 μM. Chemical analysis revealed that DFP and edaravone react immediately in aqueous solution and produce a new compound named DFP-E. DFP-E chemically reacted with NADH much faster than DFP and generated ROS, and biologically, it was much more cell-permeable than DFP. These findings collectively indicated that the combined use of DFP with edaravone produced DFP-E, which caused intracellular ROS generation and cell death. Cell death was observed in normal cells, and edaravone reacted with another Pterin Derivative to yield an ROS-generating compound. As a result, care should be taken with the clinical use of edaravone when Pterin Derivatives stay in the body.
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photodynamic effects of a novel Pterin Derivative on a pancreatic cancer cell line
Biochemical and Biophysical Research Communications, 2005Co-Authors: Hiroko Yamada, Toshiyuki Arai, Mitsuru Nonogawa, Keisuke Makino, Nobuyuki Endo, Kouhei Yamashita, Masataka Sasada, Kazuhiko Fukuda, Takashi UchiyamaAbstract:6-FormylPterin (6FP) has the potential to produce singlet oxygen ({sup 1}O{sub 2}) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the {sup 1}O{sub 2} generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate {sup 1}O{sub 2} to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable Pterin Derivatives has the potential for application in PDT.
Toshiyuki Arai - One of the best experts on this subject based on the ideXlab platform.
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the radical scavenger edaravone 3 methyl 1 phenyl 2 pyrazolin 5 one reacts with a Pterin Derivative and produces a cytotoxic substance that induces intracellular reactive oxygen species generation and cell death
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Toshiyuki Arai, Mitsuru Nonogawa, Keisuke Makino, Nobuyuki Endo, Hiroko Mori, Takashi Miyoshi, Kouhei Yamashita, Masataka Sasada, Masahiro Kakuyama, Kazuhiko FukudaAbstract:Cytotoxic effects of the combined use of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger and an approved medicine for acute brain infarction in Japan, with a Pterin Derivative, were examined in vitro. When pancreatic cancer cell line Panc-1 cells were incubated with 50 to 400 μM of a Pterin Derivative, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (DFP), and the equivalent dose of edaravone, reactive oxygen species (ROS), were generated, and cell death was induced. ROS generation and the loss of mitochondrial membrane potential (MMP) preceding cell death were simultaneously monitored using time-lapse microscopy with an ROS-sensitive dye and a probe to monitor MMP, respectively. Cell death was also estimated quantitatively by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. ROS generation and cell death were prominent when more than 100 μM of each agent was used in combination, whereas the sole use of each agent did not show any effects even at the highest dose, 400 μM. Chemical analysis revealed that DFP and edaravone react immediately in aqueous solution and produce a new compound named DFP-E. DFP-E chemically reacted with NADH much faster than DFP and generated ROS, and biologically, it was much more cell-permeable than DFP. These findings collectively indicated that the combined use of DFP with edaravone produced DFP-E, which caused intracellular ROS generation and cell death. Cell death was observed in normal cells, and edaravone reacted with another Pterin Derivative to yield an ROS-generating compound. As a result, care should be taken with the clinical use of edaravone when Pterin Derivatives stay in the body.
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hydrogen bond removal of Pterin Derivative whose structure is similar to nucleic acid bases
Nucleic acids symposium series (2004), 2005Co-Authors: Mitsuru Nonogawa, Toshiyuki Arai, Nobuyuki Endo, Seung Pil Pack, Tsutomu Kodaki, Keisuke MakinoAbstract:Pterin, an analog of guanine, is an electron transfer compound in biological systems. Among the analogs, 6-formylPterin (6FP) has been demonstrated to have many marked physiological and pharmacological activities and it is, therefore, worthwhile to elucidate whole mechanism of its activities. Unfortunately, however, 6FP is hardly soluble in water and organic solvents. Like nucleic acid bases, 6FP makes intermolecular hydrogen bonds and forms stacking structure causing such drawback nature. This has made mechanistic studies on 6FP activities extremely difficult. In this study, we carried out derivatization for 6FP and succeeded in increasing water solubility with maintaining its physiological activities.
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photodynamic effects of a novel Pterin Derivative on a pancreatic cancer cell line
Biochemical and Biophysical Research Communications, 2005Co-Authors: Hiroko Yamada, Toshiyuki Arai, Mitsuru Nonogawa, Keisuke Makino, Nobuyuki Endo, Kouhei Yamashita, Masataka Sasada, Kazuhiko Fukuda, Takashi UchiyamaAbstract:6-FormylPterin (6FP) has the potential to produce singlet oxygen ({sup 1}O{sub 2}) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the {sup 1}O{sub 2} generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate {sup 1}O{sub 2} to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable Pterin Derivatives has the potential for application in PDT.
Mitsuru Nonogawa - One of the best experts on this subject based on the ideXlab platform.
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the radical scavenger edaravone 3 methyl 1 phenyl 2 pyrazolin 5 one reacts with a Pterin Derivative and produces a cytotoxic substance that induces intracellular reactive oxygen species generation and cell death
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Toshiyuki Arai, Mitsuru Nonogawa, Keisuke Makino, Nobuyuki Endo, Hiroko Mori, Takashi Miyoshi, Kouhei Yamashita, Masataka Sasada, Masahiro Kakuyama, Kazuhiko FukudaAbstract:Cytotoxic effects of the combined use of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger and an approved medicine for acute brain infarction in Japan, with a Pterin Derivative, were examined in vitro. When pancreatic cancer cell line Panc-1 cells were incubated with 50 to 400 μM of a Pterin Derivative, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (DFP), and the equivalent dose of edaravone, reactive oxygen species (ROS), were generated, and cell death was induced. ROS generation and the loss of mitochondrial membrane potential (MMP) preceding cell death were simultaneously monitored using time-lapse microscopy with an ROS-sensitive dye and a probe to monitor MMP, respectively. Cell death was also estimated quantitatively by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. ROS generation and cell death were prominent when more than 100 μM of each agent was used in combination, whereas the sole use of each agent did not show any effects even at the highest dose, 400 μM. Chemical analysis revealed that DFP and edaravone react immediately in aqueous solution and produce a new compound named DFP-E. DFP-E chemically reacted with NADH much faster than DFP and generated ROS, and biologically, it was much more cell-permeable than DFP. These findings collectively indicated that the combined use of DFP with edaravone produced DFP-E, which caused intracellular ROS generation and cell death. Cell death was observed in normal cells, and edaravone reacted with another Pterin Derivative to yield an ROS-generating compound. As a result, care should be taken with the clinical use of edaravone when Pterin Derivatives stay in the body.
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hydrogen bond removal of Pterin Derivative whose structure is similar to nucleic acid bases
Nucleic acids symposium series (2004), 2005Co-Authors: Mitsuru Nonogawa, Toshiyuki Arai, Nobuyuki Endo, Seung Pil Pack, Tsutomu Kodaki, Keisuke MakinoAbstract:Pterin, an analog of guanine, is an electron transfer compound in biological systems. Among the analogs, 6-formylPterin (6FP) has been demonstrated to have many marked physiological and pharmacological activities and it is, therefore, worthwhile to elucidate whole mechanism of its activities. Unfortunately, however, 6FP is hardly soluble in water and organic solvents. Like nucleic acid bases, 6FP makes intermolecular hydrogen bonds and forms stacking structure causing such drawback nature. This has made mechanistic studies on 6FP activities extremely difficult. In this study, we carried out derivatization for 6FP and succeeded in increasing water solubility with maintaining its physiological activities.
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photodynamic effects of a novel Pterin Derivative on a pancreatic cancer cell line
Biochemical and Biophysical Research Communications, 2005Co-Authors: Hiroko Yamada, Toshiyuki Arai, Mitsuru Nonogawa, Keisuke Makino, Nobuyuki Endo, Kouhei Yamashita, Masataka Sasada, Kazuhiko Fukuda, Takashi UchiyamaAbstract:6-FormylPterin (6FP) has the potential to produce singlet oxygen ({sup 1}O{sub 2}) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the {sup 1}O{sub 2} generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate {sup 1}O{sub 2} to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable Pterin Derivatives has the potential for application in PDT.
Nobuyuki Endo - One of the best experts on this subject based on the ideXlab platform.
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the radical scavenger edaravone 3 methyl 1 phenyl 2 pyrazolin 5 one reacts with a Pterin Derivative and produces a cytotoxic substance that induces intracellular reactive oxygen species generation and cell death
Journal of Pharmacology and Experimental Therapeutics, 2008Co-Authors: Toshiyuki Arai, Mitsuru Nonogawa, Keisuke Makino, Nobuyuki Endo, Hiroko Mori, Takashi Miyoshi, Kouhei Yamashita, Masataka Sasada, Masahiro Kakuyama, Kazuhiko FukudaAbstract:Cytotoxic effects of the combined use of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger and an approved medicine for acute brain infarction in Japan, with a Pterin Derivative, were examined in vitro. When pancreatic cancer cell line Panc-1 cells were incubated with 50 to 400 μM of a Pterin Derivative, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (DFP), and the equivalent dose of edaravone, reactive oxygen species (ROS), were generated, and cell death was induced. ROS generation and the loss of mitochondrial membrane potential (MMP) preceding cell death were simultaneously monitored using time-lapse microscopy with an ROS-sensitive dye and a probe to monitor MMP, respectively. Cell death was also estimated quantitatively by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. ROS generation and cell death were prominent when more than 100 μM of each agent was used in combination, whereas the sole use of each agent did not show any effects even at the highest dose, 400 μM. Chemical analysis revealed that DFP and edaravone react immediately in aqueous solution and produce a new compound named DFP-E. DFP-E chemically reacted with NADH much faster than DFP and generated ROS, and biologically, it was much more cell-permeable than DFP. These findings collectively indicated that the combined use of DFP with edaravone produced DFP-E, which caused intracellular ROS generation and cell death. Cell death was observed in normal cells, and edaravone reacted with another Pterin Derivative to yield an ROS-generating compound. As a result, care should be taken with the clinical use of edaravone when Pterin Derivatives stay in the body.
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hydrogen bond removal of Pterin Derivative whose structure is similar to nucleic acid bases
Nucleic acids symposium series (2004), 2005Co-Authors: Mitsuru Nonogawa, Toshiyuki Arai, Nobuyuki Endo, Seung Pil Pack, Tsutomu Kodaki, Keisuke MakinoAbstract:Pterin, an analog of guanine, is an electron transfer compound in biological systems. Among the analogs, 6-formylPterin (6FP) has been demonstrated to have many marked physiological and pharmacological activities and it is, therefore, worthwhile to elucidate whole mechanism of its activities. Unfortunately, however, 6FP is hardly soluble in water and organic solvents. Like nucleic acid bases, 6FP makes intermolecular hydrogen bonds and forms stacking structure causing such drawback nature. This has made mechanistic studies on 6FP activities extremely difficult. In this study, we carried out derivatization for 6FP and succeeded in increasing water solubility with maintaining its physiological activities.
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photodynamic effects of a novel Pterin Derivative on a pancreatic cancer cell line
Biochemical and Biophysical Research Communications, 2005Co-Authors: Hiroko Yamada, Toshiyuki Arai, Mitsuru Nonogawa, Keisuke Makino, Nobuyuki Endo, Kouhei Yamashita, Masataka Sasada, Kazuhiko Fukuda, Takashi UchiyamaAbstract:6-FormylPterin (6FP) has the potential to produce singlet oxygen ({sup 1}O{sub 2}) under UV-A radiation. In order to apply this potential to anti-cancer photodynamic therapy (PDT), we prepared a novel variant of 6FP, 2-(N,N-dimethylaminomethyleneamino)-6-formyl-3-pivaloylpteridine-4-one (6FP-tBu-DMF), and examined its photodynamic effects on a pancreatic cancer cell line, Panc-1 cells. The study using laser scanning confocal microscopy showed that the drug uptake, the {sup 1}O{sub 2} generation, and cell death were observed in the 6FP-tBu-DMF-treated cells, while these phenomena were not observed in the 6FP-treated cells. The MTT assay also showed the decrease in cell viability only in the 6FP-tBu-DMF-treated cells. Since 6FP and 6FP-tBu-DMF generate {sup 1}O{sub 2} to the same extent under UV-A radiation in aqueous solutions, these results indicated that the differences in the photodynamic effects between 6FP and 6FP-tBu-DMF were entirely attributed to the differences in the cell permeability between them. The development of cell permeable Pterin Derivatives has the potential for application in PDT.