The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
Jin-shan Tang - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of biotinylated Cardiac Glycosides for probing nur77 protein inducting pathway
Bioorganic & Medicinal Chemistry Letters, 2019Co-Authors: Dan-mei Tian, Xiao-kun Zhang, Jie Liu, Xin-sheng Yao, Jia Qiao, Yuzhou Bao, Xuelong Sun, Youwei Zhang, Jin-shan TangAbstract:Abstract The orphan nuclear receptor Nur77 (also known as TR3 or nerve growth factor-induced clone B NGFI-B) functions as a nuclear transcription factor in the regulation of target gene expression and plays a critical role in the regulation of differentiation, proliferation, apoptosis, and survival of many different cell types. Recent studies demonstrate that Nur77 also involves many important physiological and pathological processes including cancer, inflammation and immunity, cardiovascular diseases, and bone diseases. Our previous studies showed that Cardiac Glycosides could induce the expression of Nur77 protein and its translocation from the nucleus to the cytoplasm and subsequent targeting to mitochondria, leading to apoptosis of cancer cells. In order to probe the Nur77 protein inducting pathway, we designed and synthesized a series of novel biotinylated Cardiac Glycosides from β-Antiarin and α-Antiarin, two typical Cardiac Glycosides from the plant of Antiaris toxicaria. The induction of Nur77 protein expression of these biotinylated Cardiac Glycosides and their inhibitory effects on NIH-H460 cancer cell proliferation were evaluated. Results displayed that some biotinylated Cardiac Glycosides could significantly induce the expression of Nur77 protein comparable with their parent compounds β-Antiarin and α-Antiarin. Also, their streptavidin binding activities were evaluated. Among them, biotinylated Cardiac Glycosides P4b and P5a exhibited significant effect on the induction of Nur77 expression along with high binding capacity with streptavidin, suggesting that they can be used as probes for probing Nur77 protein inducting pathway.
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Cardiac Glycosides from the Seeds of Thevetia peruviana
2016Co-Authors: Dan-mei Tian, Jin-shan Tang, Huo-yun Cheng, Miao-miao Jiang, Wei-zai Shen, Xin-sheng YaoAbstract:Investigation of the seeds of Thevetia peruviana resulted in the isolation of 15 new (2–16) and 18 known (1 and 17–33) Cardiac Glycosides. Eight 19-nor-cardenolides (1–8), including two rare 19-nor-10-hydroperoxycardenolides, were obtained from T. peruviana for the first time. All the structures were characterized by NMR spectroscopy and chemical derivatization. The inhibitory effects of Cardiac Glycosides 1–33 against three cancer cell lines (human lung cancer cells, P15; human gastric cancer cells, MGC-803; and human pancreatic cancer cells, SW1990) and one normal hepatocyte cell line, LO2, were evaluated, and a preliminary structure–activity relationship is discussed. In addition, Cardiac Glycosides 1, 22, 26, and 28 were evaluated for their apoptosis-inducing activities in MGC-803 cells, showing IC50 values in the range 0.02–0.53 μM
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Cardiac Glycosides from the Seeds of Thevetia peruviana.
Journal of natural products, 2015Co-Authors: Dan-mei Tian, Jin-shan Tang, Huo-yun Cheng, Miao-miao Jiang, Wei-zai Shen, Xin-sheng YaoAbstract:Investigation of the seeds of Thevetia peruviana resulted in the isolation of 15 new (2–16) and 18 known (1 and 17–33) Cardiac Glycosides. Eight 19-nor-cardenolides (1–8), including two rare 19-nor-10-hydroperoxycardenolides, were obtained from T. peruviana for the first time. All the structures were characterized by NMR spectroscopy and chemical derivatization. The inhibitory effects of Cardiac Glycosides 1–33 against three cancer cell lines (human lung cancer cells, P15; human gastric cancer cells, MGC-803; and human pancreatic cancer cells, SW1990) and one normal hepatocyte cell line, LO2, were evaluated, and a preliminary structure–activity relationship is discussed. In addition, Cardiac Glycosides 1, 22, 26, and 28 were evaluated for their apoptosis-inducing activities in MGC-803 cells, showing IC50 values in the range 0.02–0.53 μM.
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Cardiac Glycosides from the bark of antiaris toxicaria
Fitoterapia, 2014Co-Authors: Jie Liu, Xiao-kun Zhang, Qian Liu, Jin-shan Tang, Xiao-jiang Hao, Xin-sheng Yao, Zhixing HuangAbstract:Five new Cardiac Glycosides (1-5, namely antiaroside Y-ZC) together with 19 known compounds were obtained from the bark of Antiaris toxicaria. Their chemical structures were determined by IR, HR-ESI-MS, 1D and 2D NMR (HSQC, H-1-H-1 COSY, HMBC, ROESY). The absolute configuration of sugar unit was defined by acid hydrolysis and appropriate derivatization. Compound 1 was rare 5 beta-H-10 beta-H-19-nor-cardenolide, which might derive from decarboxylative derivative of 19-COOH cardenolide. The inhibitory effects of Cardiac Glycosides 1-11 on the viability of NIH-H460 lung cancer cells and their induction of Nur77 expression were evaluated and preliminary structure-activity relationship (SAR) was also discussed. (c) 2014 Elsevier B.V. All rights reserved.
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Antiproliferative Cardiac Glycosides from the Latex of Antiaris toxicaria
Journal of natural products, 2013Co-Authors: Qian Liu, Jie Liu, Hai-feng Chen, Jin-shan Tang, Hao Gao, Guanghui Wang, Xiao-jiang Hao, Xiao-kun ZhangAbstract:Phytochemical investigation of the latex of Antiaris toxicaria resulted in the isolation of 15 new [antiarosides J-X (1-15)] and 17 known Cardiac Glycosides. The effects of the Cardiac Glycosides on apoptosis and the expression of orphan nuclear receptor Nur77 were examined in human NIH-H460 lung cancer cells. Several of the Cardiac Glycosides induced apoptosis in lung cancer cells, which was accompanied by induction of Nur77 protein expression. Treatment of cancer cells with the Cardiac Glycosides resulted in translocation of the Nur77 protein from the nucleus to the cytoplasm and subsequent targeting to mitochondria. The results show that the Cardiac Glycosides exert their apoptotic effect through the Nur77-dependent apoptotic pathway.
Jürgen Rullkötter - One of the best experts on this subject based on the ideXlab platform.
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Cardiac Glycosides from Yellow Oleander (Thevetia peruviana) seeds
Phytochemistry, 2011Co-Authors: Sarah Kohls, Barbara M. Scholz-böttcher, Jörg Teske, Patrick Zark, Jürgen RullkötterAbstract:Thevetia Cardiac Glycosides can lead to intoxication, thus they are important indicators for forensic and pharmacologic surveys. Six thevetia Cardiac Glycosides, including two with unknown structures, were isolated from the seeds of the Yellow Oleander (Thevetia peruviana (Pers.) K. Shum., Apocynaceae). LC-ESI⁺-MS(/MS) analysis under high-resolution conditions used as a qualitative survey of the primary Glycosides did not lead to fragmentation of the aglycones. Acid hydrolysis of the polar and non-volatile thevetia Glycosides under severe conditions yielded the aglycones of the thevetia Glycosides and made them amenable to GC-MS analysis. Comparison of mass spectral fragmentation patterns of the aglycones, as well as high-resolution mass spectrometric and NMR data of four of the primary thevetia Glycosides including the two unknowns, revealed the structures of the complete set of six thevetia Glycosides. The identified compounds are termed thevetin C and acetylthevetin C and differ by an 18,20-oxido-20,22-dihydro functionality from thevetin B and acetylthevetin B, respectively. The absence of an unsaturated lactone ring renders the Glycosides cardio-inactive. The procedures developed in this study and the sets of analytical data obtained will be useful for screening and structure assessment of other, particularly polar, Cardiac Glycosides.
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Method validation of a survey of thevetia Cardiac Glycosides in serum samples.
Forensic science international, 2011Co-Authors: Sarah Kohls, Barbara M. Scholz-böttcher, Jürgen Rullkötter, Jörg TeskeAbstract:A sensitive and specific liquid chromatography tandem mass spectrometry (HPLC-ESI(+)-MS/MS) procedure was developed and validated for the identification and quantification of thevetin B and further Cardiac Glycosides in human serum. The seeds of Yellow Oleander (Thevetia peruviana) contain Cardiac Glycosides that can cause serious intoxication. A mixture of six thevetia Glycosides was extracted from these seeds and characterized. Thevetin B, isolated and efficiently purified from that mixture, is the main component and can be used as evidence. Solid phase extraction (SPE) proved to be an effective sample preparation method. Digoxin-d3 was used as the internal standard. Although ion suppression occurs, the limit of detection (LOD) is 0.27 ng/ml serum for thevetin B. Recovery is higher than 94%, and accuracy and precision were proficient. Method refinement was carried out with regard to developing a general screening method for Cardiac Glycosides. The assay is linear over the range of 0.5-8 ng/ml serum. Finally, the method was applied to a case of thevetia seed ingestion.
Xin-sheng Yao - One of the best experts on this subject based on the ideXlab platform.
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design and synthesis of biotinylated Cardiac Glycosides for probing nur77 protein inducting pathway
Bioorganic & Medicinal Chemistry Letters, 2019Co-Authors: Dan-mei Tian, Xiao-kun Zhang, Jie Liu, Xin-sheng Yao, Jia Qiao, Yuzhou Bao, Xuelong Sun, Youwei Zhang, Jin-shan TangAbstract:Abstract The orphan nuclear receptor Nur77 (also known as TR3 or nerve growth factor-induced clone B NGFI-B) functions as a nuclear transcription factor in the regulation of target gene expression and plays a critical role in the regulation of differentiation, proliferation, apoptosis, and survival of many different cell types. Recent studies demonstrate that Nur77 also involves many important physiological and pathological processes including cancer, inflammation and immunity, cardiovascular diseases, and bone diseases. Our previous studies showed that Cardiac Glycosides could induce the expression of Nur77 protein and its translocation from the nucleus to the cytoplasm and subsequent targeting to mitochondria, leading to apoptosis of cancer cells. In order to probe the Nur77 protein inducting pathway, we designed and synthesized a series of novel biotinylated Cardiac Glycosides from β-Antiarin and α-Antiarin, two typical Cardiac Glycosides from the plant of Antiaris toxicaria. The induction of Nur77 protein expression of these biotinylated Cardiac Glycosides and their inhibitory effects on NIH-H460 cancer cell proliferation were evaluated. Results displayed that some biotinylated Cardiac Glycosides could significantly induce the expression of Nur77 protein comparable with their parent compounds β-Antiarin and α-Antiarin. Also, their streptavidin binding activities were evaluated. Among them, biotinylated Cardiac Glycosides P4b and P5a exhibited significant effect on the induction of Nur77 expression along with high binding capacity with streptavidin, suggesting that they can be used as probes for probing Nur77 protein inducting pathway.
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Cardiac Glycosides from the Seeds of Thevetia peruviana
2016Co-Authors: Dan-mei Tian, Jin-shan Tang, Huo-yun Cheng, Miao-miao Jiang, Wei-zai Shen, Xin-sheng YaoAbstract:Investigation of the seeds of Thevetia peruviana resulted in the isolation of 15 new (2–16) and 18 known (1 and 17–33) Cardiac Glycosides. Eight 19-nor-cardenolides (1–8), including two rare 19-nor-10-hydroperoxycardenolides, were obtained from T. peruviana for the first time. All the structures were characterized by NMR spectroscopy and chemical derivatization. The inhibitory effects of Cardiac Glycosides 1–33 against three cancer cell lines (human lung cancer cells, P15; human gastric cancer cells, MGC-803; and human pancreatic cancer cells, SW1990) and one normal hepatocyte cell line, LO2, were evaluated, and a preliminary structure–activity relationship is discussed. In addition, Cardiac Glycosides 1, 22, 26, and 28 were evaluated for their apoptosis-inducing activities in MGC-803 cells, showing IC50 values in the range 0.02–0.53 μM
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Cardiac Glycosides from the Seeds of Thevetia peruviana.
Journal of natural products, 2015Co-Authors: Dan-mei Tian, Jin-shan Tang, Huo-yun Cheng, Miao-miao Jiang, Wei-zai Shen, Xin-sheng YaoAbstract:Investigation of the seeds of Thevetia peruviana resulted in the isolation of 15 new (2–16) and 18 known (1 and 17–33) Cardiac Glycosides. Eight 19-nor-cardenolides (1–8), including two rare 19-nor-10-hydroperoxycardenolides, were obtained from T. peruviana for the first time. All the structures were characterized by NMR spectroscopy and chemical derivatization. The inhibitory effects of Cardiac Glycosides 1–33 against three cancer cell lines (human lung cancer cells, P15; human gastric cancer cells, MGC-803; and human pancreatic cancer cells, SW1990) and one normal hepatocyte cell line, LO2, were evaluated, and a preliminary structure–activity relationship is discussed. In addition, Cardiac Glycosides 1, 22, 26, and 28 were evaluated for their apoptosis-inducing activities in MGC-803 cells, showing IC50 values in the range 0.02–0.53 μM.
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Cardiac Glycosides from the bark of antiaris toxicaria
Fitoterapia, 2014Co-Authors: Jie Liu, Xiao-kun Zhang, Qian Liu, Jin-shan Tang, Xiao-jiang Hao, Xin-sheng Yao, Zhixing HuangAbstract:Five new Cardiac Glycosides (1-5, namely antiaroside Y-ZC) together with 19 known compounds were obtained from the bark of Antiaris toxicaria. Their chemical structures were determined by IR, HR-ESI-MS, 1D and 2D NMR (HSQC, H-1-H-1 COSY, HMBC, ROESY). The absolute configuration of sugar unit was defined by acid hydrolysis and appropriate derivatization. Compound 1 was rare 5 beta-H-10 beta-H-19-nor-cardenolide, which might derive from decarboxylative derivative of 19-COOH cardenolide. The inhibitory effects of Cardiac Glycosides 1-11 on the viability of NIH-H460 lung cancer cells and their induction of Nur77 expression were evaluated and preliminary structure-activity relationship (SAR) was also discussed. (c) 2014 Elsevier B.V. All rights reserved.
Eleftherios P. Diamandis - One of the best experts on this subject based on the ideXlab platform.
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Novel therapeutic applications of Cardiac Glycosides
Nature Reviews Drug Discovery, 2008Co-Authors: Ioannis Prassas, Eleftherios P. DiamandisAbstract:Cardiac Glycosides, a diverse family of naturally derived compounds that inhibit Na^+/K^+-ATPase, have been used for many years for the treatment of heart failure and atrial arrhythmia. This article discusses recent evidence highlighting additional signal transduction roles for Na^+/K^+-ATPase, and associated potential new therapeutic appplications for glycoside-based drugs in a range of diseases — most notably cancer, for which the first generation of such agents are currently in clinical trials. Cardiac Glycosides constitute a diverse family of naturally derived compounds widely known for their ability to bind to and inhibit the sodium pump. Members of this family have been used in the clinic for many years for the treatment of heart failure and atrial arrhythmia. Recent findings report additional signalling modes of action of the sodium pump and implicate Cardiac Glycosides in the regulation of several important cellular processes, including gene-expression profiling, apoptosis, proliferation and cell–cell interactions. Cancer cells are more vulnerable to the effects of these compounds compared with normal cells. The increased susceptibility of cancer cells to these compounds supports their potential use as novel antineoplastic agents. Early epidemiological studies in patients with heart failure under Cardiac glycoside treatment revealed the potential use of these drugs as novel antineoplastic agents. Accumulating studies from the past decade verify the anticancer effects of these drugs both in vitro and in vivo . The first generation of Cardiac-glycoside-based anticancer drugs is currently in clinical trials (for example, Anvirzel and UNBS1450). Novel insights into the mode of action of these drugs reveal potential therapeutic uses of these drugs for the treatment of several diseases, including cystic fibrosis, ischaemic stroke and neurodegenerative diseases. Cardiac Glycosides are a diverse family of naturally derived compounds that bind to and inhibit Na^+/K^+-ATPase. Members of this family have been in clinical use for many years for the treatment of heart failure and atrial arrhythmia, and the mechanism of their positive inotropic effect is well characterized. Exciting recent findings have suggested additional signalling modes of action of Na^+/K^+-ATPase, implicating Cardiac Glycosides in the regulation of several important cellular processes and highlighting potential new therapeutic roles for these compounds in various diseases. Perhaps most notably, the increased susceptibility of cancer cells to these compounds supports their potential use as cancer therapies, and the first generation of glycoside-based anticancer drugs are currently in clinical trials.
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novel therapeutic applications of Cardiac Glycosides
Nature Reviews Drug Discovery, 2008Co-Authors: Ioannis Prassas, Eleftherios P. DiamandisAbstract:Cardiac Glycosides are a diverse family of naturally derived compounds that bind to and inhibit Na+/K+-ATPase. Members of this family have been in clinical use for many years for the treatment of heart failure and atrial arrhythmia, and the mechanism of their positive inotropic effect is well characterized. Exciting recent findings have suggested additional signalling modes of action of Na+/K+-ATPase, implicating Cardiac Glycosides in the regulation of several important cellular processes and highlighting potential new therapeutic roles for these compounds in various diseases. Perhaps most notably, the increased susceptibility of cancer cells to these compounds supports their potential use as cancer therapies, and the first generation of glycoside-based anticancer drugs are currently in clinical trials.
Sarah Kohls - One of the best experts on this subject based on the ideXlab platform.
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Cardiac Glycosides from Yellow Oleander (Thevetia peruviana) seeds
Phytochemistry, 2011Co-Authors: Sarah Kohls, Barbara M. Scholz-böttcher, Jörg Teske, Patrick Zark, Jürgen RullkötterAbstract:Thevetia Cardiac Glycosides can lead to intoxication, thus they are important indicators for forensic and pharmacologic surveys. Six thevetia Cardiac Glycosides, including two with unknown structures, were isolated from the seeds of the Yellow Oleander (Thevetia peruviana (Pers.) K. Shum., Apocynaceae). LC-ESI⁺-MS(/MS) analysis under high-resolution conditions used as a qualitative survey of the primary Glycosides did not lead to fragmentation of the aglycones. Acid hydrolysis of the polar and non-volatile thevetia Glycosides under severe conditions yielded the aglycones of the thevetia Glycosides and made them amenable to GC-MS analysis. Comparison of mass spectral fragmentation patterns of the aglycones, as well as high-resolution mass spectrometric and NMR data of four of the primary thevetia Glycosides including the two unknowns, revealed the structures of the complete set of six thevetia Glycosides. The identified compounds are termed thevetin C and acetylthevetin C and differ by an 18,20-oxido-20,22-dihydro functionality from thevetin B and acetylthevetin B, respectively. The absence of an unsaturated lactone ring renders the Glycosides cardio-inactive. The procedures developed in this study and the sets of analytical data obtained will be useful for screening and structure assessment of other, particularly polar, Cardiac Glycosides.
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Method validation of a survey of thevetia Cardiac Glycosides in serum samples.
Forensic science international, 2011Co-Authors: Sarah Kohls, Barbara M. Scholz-böttcher, Jürgen Rullkötter, Jörg TeskeAbstract:A sensitive and specific liquid chromatography tandem mass spectrometry (HPLC-ESI(+)-MS/MS) procedure was developed and validated for the identification and quantification of thevetin B and further Cardiac Glycosides in human serum. The seeds of Yellow Oleander (Thevetia peruviana) contain Cardiac Glycosides that can cause serious intoxication. A mixture of six thevetia Glycosides was extracted from these seeds and characterized. Thevetin B, isolated and efficiently purified from that mixture, is the main component and can be used as evidence. Solid phase extraction (SPE) proved to be an effective sample preparation method. Digoxin-d3 was used as the internal standard. Although ion suppression occurs, the limit of detection (LOD) is 0.27 ng/ml serum for thevetin B. Recovery is higher than 94%, and accuracy and precision were proficient. Method refinement was carried out with regard to developing a general screening method for Cardiac Glycosides. The assay is linear over the range of 0.5-8 ng/ml serum. Finally, the method was applied to a case of thevetia seed ingestion.