The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Cláudia Maciel - One of the best experts on this subject based on the ideXlab platform.
-
Design and synthesis of new inhibitors of p53–MDM2 interaction with a Chalcone scaffold
Arabian Journal of Chemistry, 2019Co-Authors: Daniela Pereira, Raquel T. Lima, Andreia Palmeira, Hugo Seca, Joana Soares, Sara Gomes, Liliana Raimundo, Cláudia Maciel, Madalena M. M. Pinto, Emília SousaAbstract:Abstract The virtual screening of a library of Chalcone derivatives led us to the identification of potential new MDM2 ligands. The Chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two Chalcones ( 3 and 4 ) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both Chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, Chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), Chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.
-
design and synthesis of new inhibitors of p53 mdm2 interaction with a Chalcone scaffold
Arabian Journal of Chemistry, 2016Co-Authors: Daniela Pereira, Raquel T. Lima, Andreia Palmeira, Hugo Seca, Joana Soares, Sara Gomes, Liliana Raimundo, Cláudia MacielAbstract:Abstract The virtual screening of a library of Chalcone derivatives led us to the identification of potential new MDM2 ligands. The Chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two Chalcones ( 3 and 4 ) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both Chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, Chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), Chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.
Hugo Seca - One of the best experts on this subject based on the ideXlab platform.
-
Design and synthesis of new inhibitors of p53–MDM2 interaction with a Chalcone scaffold
Arabian Journal of Chemistry, 2019Co-Authors: Daniela Pereira, Raquel T. Lima, Andreia Palmeira, Hugo Seca, Joana Soares, Sara Gomes, Liliana Raimundo, Cláudia Maciel, Madalena M. M. Pinto, Emília SousaAbstract:Abstract The virtual screening of a library of Chalcone derivatives led us to the identification of potential new MDM2 ligands. The Chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two Chalcones ( 3 and 4 ) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both Chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, Chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), Chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.
-
design and synthesis of new inhibitors of p53 mdm2 interaction with a Chalcone scaffold
Arabian Journal of Chemistry, 2016Co-Authors: Daniela Pereira, Raquel T. Lima, Andreia Palmeira, Hugo Seca, Joana Soares, Sara Gomes, Liliana Raimundo, Cláudia MacielAbstract:Abstract The virtual screening of a library of Chalcone derivatives led us to the identification of potential new MDM2 ligands. The Chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two Chalcones ( 3 and 4 ) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both Chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, Chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), Chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.
Raquel T. Lima - One of the best experts on this subject based on the ideXlab platform.
-
Design and synthesis of new inhibitors of p53–MDM2 interaction with a Chalcone scaffold
Arabian Journal of Chemistry, 2019Co-Authors: Daniela Pereira, Raquel T. Lima, Andreia Palmeira, Hugo Seca, Joana Soares, Sara Gomes, Liliana Raimundo, Cláudia Maciel, Madalena M. M. Pinto, Emília SousaAbstract:Abstract The virtual screening of a library of Chalcone derivatives led us to the identification of potential new MDM2 ligands. The Chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two Chalcones ( 3 and 4 ) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both Chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, Chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), Chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.
-
design and synthesis of new inhibitors of p53 mdm2 interaction with a Chalcone scaffold
Arabian Journal of Chemistry, 2016Co-Authors: Daniela Pereira, Raquel T. Lima, Andreia Palmeira, Hugo Seca, Joana Soares, Sara Gomes, Liliana Raimundo, Cláudia MacielAbstract:Abstract The virtual screening of a library of Chalcone derivatives led us to the identification of potential new MDM2 ligands. The Chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two Chalcones ( 3 and 4 ) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both Chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, Chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), Chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.
Daniela Pereira - One of the best experts on this subject based on the ideXlab platform.
-
Design and synthesis of new inhibitors of p53–MDM2 interaction with a Chalcone scaffold
Arabian Journal of Chemistry, 2019Co-Authors: Daniela Pereira, Raquel T. Lima, Andreia Palmeira, Hugo Seca, Joana Soares, Sara Gomes, Liliana Raimundo, Cláudia Maciel, Madalena M. M. Pinto, Emília SousaAbstract:Abstract The virtual screening of a library of Chalcone derivatives led us to the identification of potential new MDM2 ligands. The Chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two Chalcones ( 3 and 4 ) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both Chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, Chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), Chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.
-
design and synthesis of new inhibitors of p53 mdm2 interaction with a Chalcone scaffold
Arabian Journal of Chemistry, 2016Co-Authors: Daniela Pereira, Raquel T. Lima, Andreia Palmeira, Hugo Seca, Joana Soares, Sara Gomes, Liliana Raimundo, Cláudia MacielAbstract:Abstract The virtual screening of a library of Chalcone derivatives led us to the identification of potential new MDM2 ligands. The Chalcones with the best docking scores obeying the Lipinski rule of five were subsequently prepared by base-catalyzed aldol reactions. The activity of these compounds as inhibitors of p53–MDM2 interaction was investigated using a yeast-based screening assay. Using this approach two Chalcones ( 3 and 4 ) were identified as putative small molecule inhibitors of p53–MDM2 interaction. The activity of both Chalcones was further investigated in a panel of human tumor cells. Chalcones 3 and 4 revealed a pronounced tumor cell growth inhibitory effect on tumor cell lines. Additionally, Chalcone 4 caused alterations in the cell cycle profile, induced apoptosis and increased the levels of p53, p21 and PUMA proteins in NCI-H460 cells. Computational docking studies allowed to predict that, like nutlin-3A (a well-known small-molecule inhibitor of p53–MDM2 interaction), Chalcones 3 and 4 bind to the p53-binding site of MDM2. The results here presented will be valuable for the structure-based design of novel and potent p53–MDM2 inhibitors.
Jungui Dai - One of the best experts on this subject based on the ideXlab platform.
-
Biocatalytic access to diverse prenylflavonoids by combining a regiospecific C-prenyltransferase and a stereospecific Chalcone isomerase
Acta Pharmaceutica Sinica B, 2018Co-Authors: Ridao Chen, Ruishan Wang, Xiao Liu, Kebo Xie, Dawei Chen, Jungui DaiAbstract:Abstract Prenylflavonoids are valuable natural products that have diverse biological properties, and are usually generated biologically by multiple metabolic enzymes in nature. In this study, structurally diverse prenylflavonoids were conveniently synthesized by enzymatic catalysis by combining GuILDT, a regiospecific Chalcone prenyltransferase, and GuCHI, a stereospecific Chalcone isomerase that has promiscuous activity for both Chalcones and prenylChalcones as substrates. Our findings provided a new approach for the synthesis of natural/unnatural bioactive prenylflavonoids, including prenylChalcones and optical prenylflavanones with Chalcone origins.
-
Biocatalytic access to diverse prenylflavonoids by combining a regiospecific C-prenyltransferase and a stereospecific Chalcone isomerase
Elsevier, 2018Co-Authors: Ridao Chen, Ruishan Wang, Xiao Liu, Kebo Xie, Dawei Chen, Jungui DaiAbstract:Prenylflavonoids are valuable natural products that have diverse biological properties, and are usually generated biologically by multiple metabolic enzymes in nature. In this study, structurally diverse prenylflavonoids were conveniently synthesized by enzymatic catalysis by combining GuILDT, a regiospecific Chalcone prenyltransferase, and GuCHI, a stereospecific Chalcone isomerase that has promiscuous activity for both Chalcones and prenylChalcones as substrates. Our findings provided a new approach for the synthesis of natural/unnatural bioactive prenylflavonoids, including prenylChalcones and optical prenylflavanones with Chalcone origins. KEY WORDS: Biocatalysis, Prenyltransferase, Chalcone isomerase, Licorice, Prenylflavonoid