Soon Hyung Woo, Sylvie Fréchette, Elie Abou Khalil, Giliane Bouchain, Arkadii Vaisburg, Naomy Bernstein, Oscar Moradei, Silvana Leit, Martin Allan, Marielle Fournel, Marie-Claude Trachy-Bourget, Zuomei Li, Jeffrey M. Besterman, Daniel Delorme,
A series of new, structurally simple trichostatin A (TSA)-like straight chain hydroxamates were prepared and evaluated for their ability to inhibit partially purified human histone deacetylase 1 (HDAC-1). Some of these compounds such as 8m, 8n, 12, and 15b exhibited potent HDAC inhibitory activity with low nanomolar IC(50) values, comparable to natural TSA. These compounds induce hyperacetylation of histones in T24 human cancer cells and significantly inhibit proliferation in various human cancer ...
Tópico(s): Peptidase Inhibition and Analysis
2002 - American Chemical Society | Journal of Medicinal Chemistry
Oscar Moradei, Leo A. Paquette,
Abstract (5S)‐(d‐Menthyloxy)‐2(5H)‐furanone 5‐Hydroxy‐2(5H)‐furanone Camphorsulfonic acid Furfural Rose Bengal
Tópico(s): Plant-derived Lignans Synthesis and Bioactivity
2003 - Wiley | Organic Syntheses
Giliane Bouchain, Silvana Leit, Sylvie Fréchette, Elie Abou Khalil, Rico Lavoie, Oscar Moradei, Soon Hyung Woo, Marielle Fournel, Pu Yan, Ann Kalita, Marie-Claude Trachy-Bourget, Carole Beaulieu, Zuomei Li, Marie‐France Robert, A. Robert MacLeod, Jeffrey M. Besterman, Daniel Delorme,
A series of sulfonamide hydroxamic acids and anilides have been synthesized and studied as histone deacetylase (HDAC) inhibitors that can induce hyperacetylation of histones in human cancer cells. The inhibition of HDAC activity represents a novel approach for intervening in cell cycle regulation. The lead candidates were screened in a panel of human tumor and normal cell lines. They selectively inhibit proliferation, cause cell cycle blocks, and induce apoptosis in human cancer cells but not in ...
Tópico(s): Protein Degradation and Inhibitors
2003 - American Chemical Society | Journal of Medicinal Chemistry
Arkadii Vaisburg, Naomy Bernstein, Sylvie Fréchette, Martin Allan, Elie Abou-Khalil, Silvana Leit, Oscar Moradei, Giliane Bouchain, Jinru Wang, Soon Hyung Woo, Marielle Fournel, Pu Yan, Marie-Claude Trachy-Bourget, Ann Kalita, Carole Beaulieu, Zuomei Li, A. Robert MacLeod, Jeffrey M. Besterman, Daniel Delorme,
Tópico(s): Protein Degradation and Inhibitors
2003 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters
Nancy Zhou, Oscar Moradei, Stéphane Raeppel, Silvana Leit, Sylvie Fréchette, Frédéric Gaudette, Isabelle Paquin, Naomy Bernstein, Giliane Bouchain, Arkadii Vaisburg, Zhiyun Jin, J. H. Gillespie, Jinru Wang, Marielle Fournel, Pu Yan, Marie-Claude Trachy-Bourget, Ann Kalita, Aihua Lu, Jubrail Rahil, A. Robert MacLeod, Zuomei Li, Jeffrey M. Besterman, Daniel Delorme,
The design, synthesis, and biological evaluation of N-(2-aminophenyl)-4-[(4-pyridin-3-ylpyrimidin-2-ylamino)methyl]benzamide 8 (MGCD0103) is described. Compound 8 is an isotype-selective small molecule histone deacetylase (HDAC) inhibitor that selectively inhibits HDACs 1-3 and 11 at submicromolar concentrations in vitro. 8 blocks cancer cell proliferation and induces histone acetylation, p21 (cip/waf1) protein expression, cell-cycle arrest, and apoptosis. 8 is orally bioavailable, has significant ...
Tópico(s): Protein Degradation and Inhibitors
2008 - American Chemical Society | Journal of Medicinal Chemistry
Oscar Moradei, Arkadii Vaisburg, Robert E. Martell,
Histone deacetylase (HDAC) inhibitors constitute a novel and growing class of anticancer agents that function by altering intracellular patterns of histone acetylation, the so-called epigenetic "histone code," thereby producing changes in cell cycle arrest, differentiation, and/or apoptosis in tumor cells. This overview describes the chemistry and preliminary characterization of recently disclosed molecules in three major classes of HDAC inhibitors: hydroxamic acids, 2-aminobenzanilides, and cyclic ...
Tópico(s): Peptidase Inhibition and Analysis
2008 - Bentham Science Publishers | Current Topics in Medicinal Chemistry
Marielle Fournel, Claire Bonfils, Yu Hou, Pu Yan, Marie-Claude Trachy-Bourget, Ann Kalita, Jianhong Liu, Aihua Lu, Nancy Z. Zhou, Marie‐France Robert, Jeffrey Gillespie, Jinru Wang, Hélène Ste-Croix, Jubrail Rahil, Sylvain Lefèbvre, Oscar Moradei, Daniel Delorme, A. Robert MacLeod, Jeffrey M. Besterman, Zuomei Li,
Nonselective inhibitors of human histone deacetylases (HDAC) are known to have antitumor activity in mice in vivo, and several of them are under clinical investigation. The first of these, Vorinostat (SAHA), has been approved for treatment of cutaneous T-cell lymphoma. Questions remain concerning which HDAC isotype(s) are the best to target for anticancer activity and whether increased efficacy and safety will result with an isotype-selective HDAC inhibitor. We have developed an isotype-selective ...
Tópico(s): Nuclear Receptors and Signaling
2008 - American Association for Cancer Research | Molecular Cancer Therapeutics
Oscar Moradei, Tammy C. Mallais, Sylvie Fréchette, Isabelle Paquin, Pierre Tessier, Silvana Leit, Marielle Fournel, Claire Bonfils, Marie-Claude Trachy-Bourget, Jianhong Liu, Theresa P. Yan, Aihua Lu, Jubrail Rahil, Jinru Wang, Sylvain Lefèbvre, Zuomei Li, Arkadii Vaisburg, Jeffrey M. Besterman,
Significant effort is being made to understand the role of HDAC isotypes in human cancer and to develop antitumor agents with better therapeutic windows. A part of this endeavor was the exploration of the 14 A internal cavity adjacent to the enzyme catalytic site, which led to the design and synthesis of compound 4 with the unusual bis(aryl)-type pharmacophore. SAR studies around this lead resulted in optimization to potent, selective, nonhydroxamic acid HDAC inhibitors.
Tópico(s): Peptidase Inhibition and Analysis
2007 - American Chemical Society | Journal of Medicinal Chemistry
Arkadii Vaisburg, Isabelle Paquin, Naomy Bernstein, Sylvie Fréchette, Frédéric Gaudette, Silvana Leit, Oscar Moradei, Stéphane Raeppel, Nancy Zhou, Giliane Bouchain, Soon Hyung Woo, Zhiyun Jin, J. H. Gillespie, Jinru Wang, Marielle Fournel, Pu Yan, Marie-Claude Trachy-Bourget, Marie‐France Robert, Aihua Lu, Jimmy Yuk, Jubrail Rahil, A. Robert MacLeod, Jeffrey M. Besterman, Zuomei Li, Daniel Delorme,
A variety of N-(2-amino-phenyl)-4-(heteroarylmethyl)-benzamides were designed and synthesized. These compounds were shown to inhibit recombinant human HDAC1 with IC50 values in the sub-micromolar range. In human cancer cells growing in culture these compounds induced hyperacetylation of histones, induced the expression of the tumor suppressor protein p21WAF1/Cip1, and inhibited cellular proliferation. Certain compounds of this class also showed in vivo activity in various human tumor xenograft models ...
Tópico(s): Peptidase Inhibition and Analysis
2007 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters
Isabelle Paquin, Stéphane Raeppel, Silvana Leit, Frédéric Gaudette, Nancy Zhou, Oscar Moradei, Oscar Saavedra, Naomy Bernstein, Franck Raeppel, Giliane Bouchain, Sylvie Fréchette, Soon Hyung Woo, Arkadii Vaisburg, Marielle Fournel, Ann Kalita, Marie‐France Robert, Aihua Lu, Marie-Claude Trachy-Bourget, Pu Yan, Jianhong Liu, Jubrail Rahil, A. Robert MacLeod, Jeffrey M. Besterman, Zuomei Li, Daniel Delorme,
Inhibition of histone deacetylases (HDAC) is emerging as a new strategy in human cancer therapy. The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides is presented herein. From the different series bearing a six-membered heteroaromatic ring studied, the s-triazine series showed the best HDAC1 enzyme and in vitro anti-proliferative activities with IC(50) values below micromolar range. Some of these compounds can also significantly reduce tumor ...
Tópico(s): Adenosine and Purinergic Signaling
2007 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters
R. Perrin, Emmanuel Cid, Sébastien Cazin, A. Sévrain, Marianna Braza, F. Moradei, G. Harran,
Tópico(s): Fluid Dynamics and Turbulent Flows
2006 - Springer Science+Business Media | Experiments in Fluids
R. Perrin, M. Braza, Emmanuel Cid, Sébastien Cazin, F. Moradei, A. Barthet, A. Sévrain, Yannick Hoarau,
Tópico(s): Aerodynamics and Fluid Dynamics Research
2006 - Springer Science+Business Media | Flow Turbulence and Combustion
Oscar Moradei, Silvana Leit, Nancy Zhou, Sylvie Fréchette, Isabelle Paquin, Stéphane Raeppel, Frédéric Gaudette, Giliane Bouchain, Soon Hyung Woo, Arkadii Vaisburg, Marielle Fournel, Ann Kalita, Aihua Lu, Marie-Claude Trachy-Bourget, Pu Yan, Jianhong Liu, Zuomei Li, Jubrail Rahil, A. Robert MacLeod, Jeffrey M. Besterman, Daniel Delorme,
Inhibition of histone deacetylases (HDACs) is emerging as a new strategy in human cancer therapy. Novel 2-aminophenyl benzamides and acrylamides, that can inhibit human HDAC enzymes and induce hyperacetylation of histones in human cancer cells, have been designed and synthesized. These compounds selectively inhibit proliferation and cause cell cycle arrest in various human cancer cells but not in normal cells. The growth inhibition of 2-aminophenyl benzamides and acrylamides against human cancer ...
Tópico(s): Epigenetics and DNA Methylation
2006 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters
Oscar Moradei, Christiane R. Maroun, Isabelle Paquin, Arkadii Vaisburg,
Histone deacetylases (HDACs) and histone acetyltransferases (HATs) are enzymes that catalyze the deacetylation and acetylation of lysine residues located in the NH(2) terminal tails of histones and non-histone proteins. Perturbation of this balance is often observed in human cancers and inhibition of HDACs has emerged as a novel therapeutic strategy against cancer. To date, more that 30 groups, academic and industrial, are involved in research related to these target enzymes. Over the past year, dozens ...
Tópico(s): Histone Deacetylase Inhibitors Research
2005 - Bentham Science Publishers | Current Medicinal Chemistry - Anti-Cancer Agents
Leo A. Paquette, Oscar Moradei, Patrick Bernardelli, Tim Lange,
The structure attributed to sclerophytin A, a cytotoxic soft coral metabolite, was synthesized in an enantioselective manner from (5S)-5-(d-menthyloxy)-2(5H)-furanone. The spectral properties and polarity of the synthetic product require that the structural assignment to the natural material be revised.
Tópico(s): Traditional and Medicinal Uses of Annonaceae
2000 - American Chemical Society | Organic Letters
Patrick Bernardelli, Oscar Moradei, Dirk Friedrich, Jiong Yang, Fabrice Gallou, Brian Dyck, Raymond W. Doskotch, Tim Lange, Leo A. Paquette,
An enantioselective synthetic route to the thermodynamically most stable diastereomer of the structure assigned to sclerophytin A (5) has been realized. The required tricyclic ketone 33 was prepared by sequential Tebbe−Claisen rearrangement of lactones 29 and 30, which originated from the Diels−Alder cycloaddition of Danishefsky's diene to (5S)-5-(d-menthyloxy)-2(5H)-furanone (14). An allyl and a cyano group were introduced into the resulting adduct by means of stereocontrolled allylindation under ...
Tópico(s): Biological Activity of Diterpenoids and Biflavonoids
2001 - American Chemical Society | Journal of the American Chemical Society
K. C. Nicolaou, Xianhai Huang, Nicolas Giuseppone, Paraselli Bheema Rao, Marco Bella, Mali V. Reddy, Scott A. Snyder,
... a related example, see: P. Bernardelli, O. M. Moradei, D. Friedrich, J. Yang, F. Gallou, B. P. ...
Tópico(s): Cyclopropane Reaction Mechanisms
2001 - Wiley | Angewandte Chemie International Edition
Lorna H. Mitchell, Allison E. Drew, Scott Ribich, Nathalie Rioux, Kerren K. Swinger, Suzanne L. Jacques, Trupti Lingaraj, P. Ann Boriack‐Sjodin, Nigel J. Waters, Tim J. Wigle, Oscar Moradei, Lei Jin, Thomas V. Riera, Margaret Porter-Scott, Mikel P. Moyer, J. Joshua Smith, Richard Chesworth, Robert A. Copeland,
A novel aryl pyrazole series of arginine methyltransferase inhibitors has been identified. Synthesis of analogues within this series yielded the first potent, selective, small molecule PRMT6 inhibitor tool compound, EPZ020411. PRMT6 overexpression has been reported in several cancer types suggesting that inhibition of PRMT6 activity may have therapeutic utility. Identification of EPZ020411 provides the field with the first small molecule tool compound for target validation studies. EPZ020411 shows ...
Tópico(s): Epigenetics and DNA Methylation
2015 - American Chemical Society | ACS Medicinal Chemistry Letters
P. Ann Boriack‐Sjodin, Lei Jin, Suzanne L. Jacques, Allison E. Drew, Chris Sneeringer, Margaret Porter Scott, Mikel P. Moyer, Scott Ribich, Oscar Moradei, Robert A. Copeland,
Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine N-methyltransferase (PRMT) enzyme that has been implicated in a variety of cancers. CARM1 is known to methylate histone H3 and nonhistone substrates. To date, several crystal structures of CARM1 have been solved, including structures with small molecule inhibitors, but no ternary structures with nucleoside and peptide substrates have been reported. Here, the crystal structures of human CARM1 with the S-adenosylmethione ( ...
Tópico(s): Epigenetics and DNA Methylation
2015 - American Chemical Society | ACS Chemical Biology
Christopher J. Bungard, Peter Williams, Jeanine Ballard, David Jonathan Bennett, Christian Beaulieu, Carolyn Bahnck-Teets, Steve S. Carroll, Ronald K. Chang, David C. Dubost, John F. Fay, Tracy L. Diamond, Thomas J. Greshock, Hao Li, M. Katharine Holloway, Peter J. Felock, Jennifer J. Gesell, Hua-Poo Su, Jesse J. Manikowski, Daniel J. McKay, Mike Miller, Xu Min, Carmela Molinaro, Oscar Moradei, Philippe G. Nantermet, Christian Nadeau, Rosa I. Sánchez, Tummanapalli Satyanarayana, William D. Shipe, Sanjay K. Singh, Vouy Linh Truong, S. Vijayasaradhi, Catherine M. Wiscount, Joseph P. Vacca, Sheldon N. Crane, John A. McCauley,
A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.
Tópico(s): HIV Research and Treatment
2016 - American Chemical Society | ACS Medicinal Chemistry Letters
Allison E. Drew, Oscar Moradei, Suzanne L. Jacques, Nathalie Rioux, Ann Boriack-Sjodin, Christina J. Allain, Margaret Porter Scott, Lei Jin, Alejandra Raimondi, Jessica L. Handler, Heidi M. Ott, Ryan G. Kruger, Michael T. McCabe, Christopher J. Sneeringer, Thomas V. Riera, Gideon Shapiro, Nigel J. Waters, Lorna H. Mitchell, Kenneth W. Duncan, Mikel P. Moyer, Robert A. Copeland, J. Joshua Smith, Richard Chesworth, Scott Ribich,
CARM1 is an arginine methyltransferase with diverse histone and non-histone substrates implicated in the regulation of cellular processes including transcriptional co-activation and RNA processing. CARM1 overexpression has been reported in multiple cancer types and has been shown to modulate oncogenic pathways in in vitro studies. Detailed understanding of the mechanism of action of CARM1 in oncogenesis has been limited by a lack of selective tool compounds, particularly for in vivo studies. We ...
Tópico(s): Protein Degradation and Inhibitors
2017 - Nature Portfolio | Scientific Reports
Donghang Cheng, Guozhen Gao, Alessandra Di Lorenzo, Sandrine Jayne, Michael O. Hottiger, Stéphane Richard, Mark T. Bedford,
... P.A. Waters N.J. Wigle T.J. Moradei O. Jin L. Riera T. Porter-Scott M. ...
Tópico(s): Epigenetics and DNA Methylation
2020 - Elsevier BV | Journal of Biological Chemistry
Sylvie Fréchette, Silvana Leit, Soon Hyung Woo, Guillaume Lapointe, Guillaume Jeannotte, Oscar Moradei, Isabelle Paquin, Giliane Bouchain, Stéphane Raeppel, Frédéric Gaudette, Nancy Zhou, Arkadii Vaisburg, Marielle Fournel, Pu Yan, Marie-Claude Trachy-Bourget, Ann Kalita, Marie‐France Robert, Aihua Lu, Jubrail Rahil, A. Robert MacLeod, Jeffrey M. Besterman, Zuomei Li, Daniel Delorme,
The synthesis and biological evaluation of a variety of 4-(heteroarylaminomethyl)-N-(2-aminophenyl)-benzamides and their analogs is described. Some of these compounds were shown to inhibit HDAC1 with IC50 values below the micromolar range, induce hyperacetylation of histones, upregulate expression of the tumor suppressor p21WAF1/Cip1, and inhibit proliferation of human cancer cells. In addition, certain compounds of this class were active in several human tumor xenograft models in vivo.
Tópico(s): Peptidase Inhibition and Analysis
2007 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters
Oscar Moradei, Cecile du Mortier, Alicia Fernández Cirelli, Joachim Thiem,
Abstract The stereospecific synthesis of methyl 3-O-benzoyl-6-O-(tert-butyldiphenylsilyl)-2-deoxy-α-d-erythro-hexopyranosid-4-ulose (5) - a Thromboxane B2 (TXB2) precursor -starting from D-galactose is described. Facile and established methods including selective benzoylation, oxidation-elimination and a stereocontrolled hydrogenation (Pd/charcoal) were employed effectively.
Tópico(s): Diet, Metabolism, and Disease
1995 - Taylor & Francis | Journal of Carbohydrate Chemistry
Oscar Moradei, Cecile du Mortier, Oscar Varela, Rosa M. de Lederkremer,
ABSTRACT Hydrogenolysis of 2,3,5-tri-O-benzoyl-6-O-trityl-D-galactono-1,4-lactone (2) gave the corresponding 3-deoxy-D-xylo-hexono-1,4-lactone derivative (3), which on treatment with HBr in acetic acid afforded 2,5-di-O-benzoyl-6-bromo-3,6-dideoxy-D-xylo-hexono 1,4-lactone (4). Hydrogenation of 4 led to 3,6-dideoxy-D-xylo-hexono-1,4-lactone dibenzoate (6). The overall yield of 6 from D-galactono-1, 4-lactone (1) was about 59%. Alternatively, compound 6 was prepared (67% overall yield from 1) by hydrogenolysis ...
Tópico(s): Phytochemical Studies and Bioactivities
1991 - Taylor & Francis | Journal of Carbohydrate Chemistry
L. Pinotti, Sharon Mazzoleni, Andrea Moradei, Peng Lin, Alice Luciano,
Following the promotion of animal welfare awareness, modern meat production should be applied ethically and sustainably. Alternative circular feeds such as algae, insects, agro-industrial by-products (AIBPs) and former food products (FFPs) play a key role to re-define the current meat production system. This review highlights the effects of feed ingredients mentioned above on red meat quality, from a blue-bio/circular economy point of view. The results show that when algae are added in adequate amounts, ...
Tópico(s): Food Industry and Aquatic Biology
2023 - Taylor & Francis | Italian Journal of Animal Science
Giacomo Grassi, Corinna Moradei, Chiara Cecchelli,
Background: Although in 2017 a repetitive transcranial magnetic stimulation (rTMS) protocol received Food and Drug Administration approval for the first time for the treatment of obsessive–compulsive disorder (OCD), which neural target and which protocol should be used for OCD are still debated. The aim of the present study was to perform a systematic review and meta-analysis of the available open and sham-controlled trials. Methods: The primary analysis included a pairwise meta-analysis (over 31 trials), ...
Tópico(s): Eating Disorders and Behaviors
2023 - Multidisciplinary Digital Publishing Institute | Life
Stéphane Raeppel, Nancy Zhou, Frédéric Gaudette, Silvana Leit, Isabelle Paquin, Guillaume Larouche, Oscar Moradei, Sylvie Fréchette, Ljubomir Isakovic, Daniel Delorme, Marielle Fournel, Ann Kalita, Aihua Lu, Marie-Claude Trachy-Bourget, Pu Yan, Jianhong Liu, Jubrail Rahil, Jinru Wang, Jeffrey M. Besterman, Koji Murakami, Zuomei Li, Arkadii Vaisburg,
Analogues of the clinical compound MGCD0103 (A) were designed and synthesized. These compounds inhibit recombinant human HDAC1 with IC(50) values in the sub-micromolar range. In human cancer cells growing in culture these compounds induce hyperacetylation of histones, cause expression of the tumor suppressor protein p21(WAF1/CIP1), and inhibit cellular proliferation. Lead molecule of the series, compound 25 is metabolically stable, possesses favorable pharmacokinetic characteristics and is orally ...
Tópico(s): Peptidase Inhibition and Analysis
2008 - Elsevier BV | Bioorganic & Medicinal Chemistry Letters
Oscar Moradei, Silvana Leit, Cecile du Mortier, Alicia Fernández Cirelli, Joachim Thiem,
Abstract Methanolysis of acylated carbohydrate derivatives was effectively performed using tertiary amines in the absence of water at room temperature. The reaction was performed with acetylated and benzoylated alditols, aldoses, lactones, orthoesters, glycosides, and disaccharides. N-methyl-pyrrolidine proved to be especially suitable for synthetic purposes and deacylated compounds were obtained in excellent yields. The mild conditions employed and the minimum work-up needed make this method appropriate ...
Tópico(s): Chemical Synthesis and Analysis
1993 - Taylor & Francis | Journal of Carbohydrate Chemistry
Oscar Moradei, Cecile du Mortier, Alicia Fernández Cirelli,
The preparation of 6-O-(tert-butyldiphenylsilyl)-α-D-glucopyranose 1,2,4-orthoacetate from 1,2-O-(1-exo-methoxyethylidene)-α-D-glucopyranose by acid catalyzed intramolecular orthotransesterification is described.A mechanism for the reaction is proposed.
Tópico(s): Biofuel production and bioconversion
2005 - ARKAT USA, Inc. | ARKIVOC