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Marc Litaudon - One of the best experts on this subject based on the ideXlab platform.
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Pentacyclic polyketides from Endiandra kingiana as inhibitors of the Bcl-Xl/Bak interaction.
Phytochemistry, 2011Co-Authors: Aurélie Leverrier, Khalijah Awang, Françoise Guéritte, Marc LitaudonAbstract:An in vitro biological screening of Malaysian plants allowed the selection of several species with a significant binding affinity for the antiapoptotic Protein Bcl-Xl. The chemical investigation of Endiandra kingiana led to the isolation of a series of polyketides named kingianins A-N, having a pentacyclic carbon skeleton described for the first time in nature. Fourteen compounds were isolated as racemic mixtures, and characterized by mass spectrometryand extensive one- and two-dimensional NMR spectroscopy. The (-) and (+) enantiomers of kingianins A and G-L were separated using chiral HPLC, and the absolute configuration of four of them was clearly established by CD analysis. The levorotatory enantiomers showed the more potent binding affinity for Bcl-Xl with Ki ranging from 1.0 to 12μM.
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Rearranged diterpenoids from the biotransformation of ent-trachyloban-18-oic acid by Rhizopus arrhizus.
Journal of Natural Products, 2010Co-Authors: Aurélie Leverrier, Claudine Servy, Jamal Ouazzani, Mat Ropi Mukhtar, Marietherese Martin, Khalijah Awang, Françoise Guéritte, Pascal Retailleau, Marc LitaudonAbstract:In our search for inhibitors of the antiapoptotic Protein Bcl-Xl, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4beta-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-Xl. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC(50) values between 10 and 30 microM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3-7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3-8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-Xl.
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rearranged diterpenoids from the biotransformation of ent trachyloban 18 oic acid by rhizopus arrhizus
Journal of Natural Products, 2010Co-Authors: Aurélie Leverrier, Claudine Servy, Jamal Ouazzani, Mat Ropi Mukhtar, Marietherese Martin, Khalijah Awang, Françoise Guéritte, Pascal Retailleau, Marc LitaudonAbstract:In our search for inhibitors of the antiapoptotic Protein Bcl-Xl, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4β-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-Xl. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC50 values between 10 and 30 μM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3−7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3−8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-Xl.
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Cytotoxic pentacyclic triterpenoids from Combretum sundaicum and Lantana camara as inhibitors of Bcl-Xl/BakBH3 domain peptide interaction.
Journal of natural products, 2009Co-Authors: Marc Litaudon, Pascal Retailleau, Olivier Nosjean, Jean A. Boutin, Claire Jolly, Catherine Le Callonec, Dao Din Cuong, Van Hung Nguyen, Bruno Pfeiffer, Françoise GuéritteAbstract:In an effort to discover potent inhibitors of the antiapoptotic Protein Bcl-Xl, a systematic in vitro evaluation was undertaken on extracts prepared from various parts of Vietnamese plants. The ethyl acetate extracts obtained from the leaves and flowers of Combretum sundaicum and the leaves of Lantana camara were selected for their interaction with the Bcl-Xl/Bak association. Bioassay-guided purification of these species led to the isolation of 15 pentacyclic triterpenoids (1-15) possessing olean-12-en-28-oic acid and olean-12-en-29-oic acid aglycons, of which compounds 1-6 and 8-10 are new. Five compounds exhibited binding activity with K(i) values between 5.3 and 17.8 microM. The cytotoxic activity of 1-15 was also evaluated on various cancer cell lines.
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A Dimeric sesquiterpenoid from a Malaysian Meiogyne as a new inhibitor of Bcl-Xl/BakBH3 domain peptide interaction.
Journal of natural products, 2009Co-Authors: Marc Litaudon, Marietherese Martin, Khalijah Awang, Hadjira Bousserouel, Olivier Nosjean, Marie Elise Tran Huu Dau, Hamid A. Hadi, Jean A. Boutin, Thierry Sévenet, Françoise GuéritteAbstract:In an effort to find potent inhibitors of the antiapoptotic Protein Bcl-Xl, a systematic in vitro evaluation was undertaken on 1470 Malaysian plant extracts. The ethyl acetate extract obtained from the bark of Meiogyne cylindrocarpa was selected for its interaction with the Bcl-Xl/Bak association. Bioassay-guided purification of this species led to the isolation of two new dimeric sesquiterpenoids (1 and 2) possessing an unprecedented substituted cis-decalin carbon skeleton. Meiogynin A (1) showed the strongest activity with a K(i) of 10.8 +/- 3.1 microM.
Françoise Guéritte - One of the best experts on this subject based on the ideXlab platform.
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Pentacyclic polyketides from Endiandra kingiana as inhibitors of the Bcl-Xl/Bak interaction.
Phytochemistry, 2011Co-Authors: Aurélie Leverrier, Khalijah Awang, Françoise Guéritte, Marc LitaudonAbstract:An in vitro biological screening of Malaysian plants allowed the selection of several species with a significant binding affinity for the antiapoptotic Protein Bcl-Xl. The chemical investigation of Endiandra kingiana led to the isolation of a series of polyketides named kingianins A-N, having a pentacyclic carbon skeleton described for the first time in nature. Fourteen compounds were isolated as racemic mixtures, and characterized by mass spectrometryand extensive one- and two-dimensional NMR spectroscopy. The (-) and (+) enantiomers of kingianins A and G-L were separated using chiral HPLC, and the absolute configuration of four of them was clearly established by CD analysis. The levorotatory enantiomers showed the more potent binding affinity for Bcl-Xl with Ki ranging from 1.0 to 12μM.
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Biomimetic total synthesis of meiogynin A, an inhibitor of Bcl-Xl and Bak interaction.
The Journal of organic chemistry, 2010Co-Authors: Dalia Fomekong Fotsop, Aurélie Leverrier, Fanny Roussi, Anne Bretéché, Françoise GuéritteAbstract:A short, convergent, and selective synthesis of meiogynin A, an inhibitor of the antiapoptotic Protein Bcl-Xl, has been performed. This synthesis, based on a biomimetic approach, allowed the determination of its absolute configuration. Three isomers of meiogynin A have also been elaborated. One of these was found to be three times more potent than the natural compound.
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Rearranged diterpenoids from the biotransformation of ent-trachyloban-18-oic acid by Rhizopus arrhizus.
Journal of Natural Products, 2010Co-Authors: Aurélie Leverrier, Claudine Servy, Jamal Ouazzani, Mat Ropi Mukhtar, Marietherese Martin, Khalijah Awang, Françoise Guéritte, Pascal Retailleau, Marc LitaudonAbstract:In our search for inhibitors of the antiapoptotic Protein Bcl-Xl, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4beta-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-Xl. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC(50) values between 10 and 30 microM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3-7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3-8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-Xl.
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rearranged diterpenoids from the biotransformation of ent trachyloban 18 oic acid by rhizopus arrhizus
Journal of Natural Products, 2010Co-Authors: Aurélie Leverrier, Claudine Servy, Jamal Ouazzani, Mat Ropi Mukhtar, Marietherese Martin, Khalijah Awang, Françoise Guéritte, Pascal Retailleau, Marc LitaudonAbstract:In our search for inhibitors of the antiapoptotic Protein Bcl-Xl, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4β-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-Xl. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC50 values between 10 and 30 μM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3−7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3−8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-Xl.
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Cytotoxic pentacyclic triterpenoids from Combretum sundaicum and Lantana camara as inhibitors of Bcl-Xl/BakBH3 domain peptide interaction.
Journal of natural products, 2009Co-Authors: Marc Litaudon, Pascal Retailleau, Olivier Nosjean, Jean A. Boutin, Claire Jolly, Catherine Le Callonec, Dao Din Cuong, Van Hung Nguyen, Bruno Pfeiffer, Françoise GuéritteAbstract:In an effort to discover potent inhibitors of the antiapoptotic Protein Bcl-Xl, a systematic in vitro evaluation was undertaken on extracts prepared from various parts of Vietnamese plants. The ethyl acetate extracts obtained from the leaves and flowers of Combretum sundaicum and the leaves of Lantana camara were selected for their interaction with the Bcl-Xl/Bak association. Bioassay-guided purification of these species led to the isolation of 15 pentacyclic triterpenoids (1-15) possessing olean-12-en-28-oic acid and olean-12-en-29-oic acid aglycons, of which compounds 1-6 and 8-10 are new. Five compounds exhibited binding activity with K(i) values between 5.3 and 17.8 microM. The cytotoxic activity of 1-15 was also evaluated on various cancer cell lines.
Aurélie Leverrier - One of the best experts on this subject based on the ideXlab platform.
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Pentacyclic polyketides from Endiandra kingiana as inhibitors of the Bcl-Xl/Bak interaction.
Phytochemistry, 2011Co-Authors: Aurélie Leverrier, Khalijah Awang, Françoise Guéritte, Marc LitaudonAbstract:An in vitro biological screening of Malaysian plants allowed the selection of several species with a significant binding affinity for the antiapoptotic Protein Bcl-Xl. The chemical investigation of Endiandra kingiana led to the isolation of a series of polyketides named kingianins A-N, having a pentacyclic carbon skeleton described for the first time in nature. Fourteen compounds were isolated as racemic mixtures, and characterized by mass spectrometryand extensive one- and two-dimensional NMR spectroscopy. The (-) and (+) enantiomers of kingianins A and G-L were separated using chiral HPLC, and the absolute configuration of four of them was clearly established by CD analysis. The levorotatory enantiomers showed the more potent binding affinity for Bcl-Xl with Ki ranging from 1.0 to 12μM.
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Biomimetic total synthesis of meiogynin A, an inhibitor of Bcl-Xl and Bak interaction.
The Journal of organic chemistry, 2010Co-Authors: Dalia Fomekong Fotsop, Aurélie Leverrier, Fanny Roussi, Anne Bretéché, Françoise GuéritteAbstract:A short, convergent, and selective synthesis of meiogynin A, an inhibitor of the antiapoptotic Protein Bcl-Xl, has been performed. This synthesis, based on a biomimetic approach, allowed the determination of its absolute configuration. Three isomers of meiogynin A have also been elaborated. One of these was found to be three times more potent than the natural compound.
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Rearranged diterpenoids from the biotransformation of ent-trachyloban-18-oic acid by Rhizopus arrhizus.
Journal of Natural Products, 2010Co-Authors: Aurélie Leverrier, Claudine Servy, Jamal Ouazzani, Mat Ropi Mukhtar, Marietherese Martin, Khalijah Awang, Françoise Guéritte, Pascal Retailleau, Marc LitaudonAbstract:In our search for inhibitors of the antiapoptotic Protein Bcl-Xl, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4beta-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-Xl. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC(50) values between 10 and 30 microM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3-7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3-8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-Xl.
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rearranged diterpenoids from the biotransformation of ent trachyloban 18 oic acid by rhizopus arrhizus
Journal of Natural Products, 2010Co-Authors: Aurélie Leverrier, Claudine Servy, Jamal Ouazzani, Mat Ropi Mukhtar, Marietherese Martin, Khalijah Awang, Françoise Guéritte, Pascal Retailleau, Marc LitaudonAbstract:In our search for inhibitors of the antiapoptotic Protein Bcl-Xl, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4β-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-Xl. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC50 values between 10 and 30 μM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3−7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3−8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-Xl.
Beat W. Schäfer - One of the best experts on this subject based on the ideXlab platform.
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transcriptional modulation of the anti apoptotic Protein Bcl Xl by the paired box transcription factors pax3 and pax3 fkhr
Oncogene, 2000Co-Authors: Christiane Margue, Michele Bernasconi, Frederic G. Barr, Beat W. SchäferAbstract:The aberrant expression of the transcription factors PAX3 and PAX3/FKHR associated with rhabdomyosarcoma (RMS), solid tumors displaying muscle cell features, suggests that these Proteins play an important role in the pathogenesis of RMS. We could previously demonstrate that one of the oncogenic functions of PAX3 and PAX3/FKHR in RMS is protection from apoptosis. Bcl-Xl is a prominent anti-apoptotic Protein present in normal skeletal muscle and RMS cells. In the present study, we establish that Bcl-Xl is transcriptionally modulated by PAX3 and PAX3/FKHR, since enhanced expression of both PAX Proteins stimulates transcription of endogenous Bcl-Xl mRNA in a cell type specific manner. Further, we present evidence that both PAX3 and PAX3/FKHR can transcriptionally activate the Bcl-x gene promoter in cotransfection assays. Using electrophoretic mobility shift assays, an ATTA binding site for PAX3 and PAX3/FKHR could be localized in the upstream promoter region (position −42 to −39). Finally, ectopic overexpression of either PAX3, PAX3/FKHR or Bcl-Xl can rescue tumor cells from apoptosis induced by antisense treatment. These results suggest that at least part of the anti-apoptotic effect of PAX3 and PAX3/FKHR is mediated through direct transcriptional modulation of the prominent anti-apoptotic Protein Bcl-Xl.
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Transcriptional modulation of the anti-apoptotic Protein Bcl-Xl by the paired box transcription factors PAX3 and PAX3/FKHR.
Oncogene, 2000Co-Authors: Christiane Margue, Michele Bernasconi, Frederic G. Barr, Beat W. SchäferAbstract:The aberrant expression of the transcription factors PAX3 and PAX3/FKHR associated with rhabdomyosarcoma (RMS), solid tumors displaying muscle cell features, suggests that these Proteins play an important role in the pathogenesis of RMS. We could previously demonstrate that one of the oncogenic functions of PAX3 and PAX3/FKHR in RMS is protection from apoptosis. Bcl-Xl is a prominent anti-apoptotic Protein present in normal skeletal muscle and RMS cells. In the present study, we establish that Bcl-Xl is transcriptionally modulated by PAX3 and PAX3/FKHR, since enhanced expression of both PAX Proteins stimulates transcription of endogenous Bcl-Xl mRNA in a cell type specific manner. Further, we present evidence that both PAX3 and PAX3/FKHR can transcriptionally activate the Bcl-x gene promoter in cotransfection assays. Using electrophoretic mobility shift assays, an ATTA binding site for PAX3 and PAX3/FKHR could be localized in the upstream promoter region (position −42 to −39). Finally, ectopic overexpression of either PAX3, PAX3/FKHR or Bcl-Xl can rescue tumor cells from apoptosis induced by antisense treatment. These results suggest that at least part of the anti-apoptotic effect of PAX3 and PAX3/FKHR is mediated through direct transcriptional modulation of the prominent anti-apoptotic Protein Bcl-Xl.
Khalijah Awang - One of the best experts on this subject based on the ideXlab platform.
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Pentacyclic polyketides from Endiandra kingiana as inhibitors of the Bcl-Xl/Bak interaction.
Phytochemistry, 2011Co-Authors: Aurélie Leverrier, Khalijah Awang, Françoise Guéritte, Marc LitaudonAbstract:An in vitro biological screening of Malaysian plants allowed the selection of several species with a significant binding affinity for the antiapoptotic Protein Bcl-Xl. The chemical investigation of Endiandra kingiana led to the isolation of a series of polyketides named kingianins A-N, having a pentacyclic carbon skeleton described for the first time in nature. Fourteen compounds were isolated as racemic mixtures, and characterized by mass spectrometryand extensive one- and two-dimensional NMR spectroscopy. The (-) and (+) enantiomers of kingianins A and G-L were separated using chiral HPLC, and the absolute configuration of four of them was clearly established by CD analysis. The levorotatory enantiomers showed the more potent binding affinity for Bcl-Xl with Ki ranging from 1.0 to 12μM.
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Rearranged diterpenoids from the biotransformation of ent-trachyloban-18-oic acid by Rhizopus arrhizus.
Journal of Natural Products, 2010Co-Authors: Aurélie Leverrier, Claudine Servy, Jamal Ouazzani, Mat Ropi Mukhtar, Marietherese Martin, Khalijah Awang, Françoise Guéritte, Pascal Retailleau, Marc LitaudonAbstract:In our search for inhibitors of the antiapoptotic Protein Bcl-Xl, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4beta-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-Xl. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC(50) values between 10 and 30 microM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3-7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3-8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-Xl.
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rearranged diterpenoids from the biotransformation of ent trachyloban 18 oic acid by rhizopus arrhizus
Journal of Natural Products, 2010Co-Authors: Aurélie Leverrier, Claudine Servy, Jamal Ouazzani, Mat Ropi Mukhtar, Marietherese Martin, Khalijah Awang, Françoise Guéritte, Pascal Retailleau, Marc LitaudonAbstract:In our search for inhibitors of the antiapoptotic Protein Bcl-Xl, investigation of Xylopia caudata afforded a new diterpenoid, ent-trachyloban-4β-ol (2), and five known ent-trachylobane or ent-atisane compounds. Only ent-trachyloban-18-oic acid (1) exhibited weak binding activity to Bcl-Xl. These compounds exhibited cytotoxicity against KB and HCT-116 cell lines with IC50 values between 10 and 30 μM. Bioconversion of compound 1 by Rhizopus arrhizus afforded new hydroxylated metabolites (3−7) of the ent-trachylobane and ent-kaurene type and compound 8, with a rearranged pentacyclic carbon framework that was named rhizopene. Compounds 3−8 were noncytotoxic to the two cancer cell lines, and compounds 3 and 5 exhibited only weak binding affinity for Bcl-Xl.
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A Dimeric sesquiterpenoid from a Malaysian Meiogyne as a new inhibitor of Bcl-Xl/BakBH3 domain peptide interaction.
Journal of natural products, 2009Co-Authors: Marc Litaudon, Marietherese Martin, Khalijah Awang, Hadjira Bousserouel, Olivier Nosjean, Marie Elise Tran Huu Dau, Hamid A. Hadi, Jean A. Boutin, Thierry Sévenet, Françoise GuéritteAbstract:In an effort to find potent inhibitors of the antiapoptotic Protein Bcl-Xl, a systematic in vitro evaluation was undertaken on 1470 Malaysian plant extracts. The ethyl acetate extract obtained from the bark of Meiogyne cylindrocarpa was selected for its interaction with the Bcl-Xl/Bak association. Bioassay-guided purification of this species led to the isolation of two new dimeric sesquiterpenoids (1 and 2) possessing an unprecedented substituted cis-decalin carbon skeleton. Meiogynin A (1) showed the strongest activity with a K(i) of 10.8 +/- 3.1 microM.
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A Dimeric Sesquiterpenoid from a Malaysian Meiogyne as a New Inhibitor of Bcl-Xl/BakBH3 Domain Peptide Interaction ( perpendicular).
2009Co-Authors: Marc Litaudon, Marietherese Martin, Khalijah Awang, Hadjira Bousserouel, Olivier Nosjean, Marie Elise Tran Huu Dau, Hamid A. Hadi, Jean A. Boutin, Thierry Sévenet, Françoise GuéritteAbstract:In an effort to find potent inhibitors of the antiapoptotic Protein Bcl-Xl, a systematic in vitro evaluation was undertaken on 1470 Malaysian plant extracts. The ethyl acetate extract obtained from the bark of Meiogyne cylindrocarpa was selected for its interaction with the Bcl-Xl/Bak association. Bioassay-guided purification of this species led to the isolation of two new dimeric sesquiterpenoids (1 and 2) possessing an unprecedented substituted cis-decalin carbon skeleton. Meiogynin A (1) showed the strongest activity with a K(i) of 10.8 +/- 3.1 muM.
