The Experts below are selected from a list of 123 Experts worldwide ranked by ideXlab platform
Keiji Maruoka - One of the best experts on this subject based on the ideXlab platform.
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Practical Approach for Asymmetric Hydroxyamination of Aldehydes with in Situ Generated Nitrosocarbonyl Compounds: Application to One-Pot Synthesis of Chiral Allylamines
Organic letters, 2014Co-Authors: Taichi Kano, Fumitaka Shirozu, Keiji MaruokaAbstract:The highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from a Hydroxamic Acid Derivative was realized by simple and readily available chiral amine catalysts. The resulting hydroxyamination products were readily converted to the corresponding chiral 1,2-aminoalcohol or allylamine Derivatives in one pot.
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Practical Approach for Asymmetric Hydroxyamination of Aldehydes with in Situ Generated Nitrosocarbonyl Compounds: Application to One-Pot Synthesis of Chiral Allylamines
2014Co-Authors: Taichi Kano, Fumitaka Shirozu, Keiji MaruokaAbstract:The highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from a Hydroxamic Acid Derivative was realized by simple and readily available chiral amine catalysts. The resulting hydroxyamination products were readily converted to the corresponding chiral 1,2-aminoalcohol or allylamine Derivatives in one pot
Taichi Kano - One of the best experts on this subject based on the ideXlab platform.
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Practical Approach for Asymmetric Hydroxyamination of Aldehydes with in Situ Generated Nitrosocarbonyl Compounds: Application to One-Pot Synthesis of Chiral Allylamines
Organic letters, 2014Co-Authors: Taichi Kano, Fumitaka Shirozu, Keiji MaruokaAbstract:The highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from a Hydroxamic Acid Derivative was realized by simple and readily available chiral amine catalysts. The resulting hydroxyamination products were readily converted to the corresponding chiral 1,2-aminoalcohol or allylamine Derivatives in one pot.
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Practical Approach for Asymmetric Hydroxyamination of Aldehydes with in Situ Generated Nitrosocarbonyl Compounds: Application to One-Pot Synthesis of Chiral Allylamines
2014Co-Authors: Taichi Kano, Fumitaka Shirozu, Keiji MaruokaAbstract:The highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from a Hydroxamic Acid Derivative was realized by simple and readily available chiral amine catalysts. The resulting hydroxyamination products were readily converted to the corresponding chiral 1,2-aminoalcohol or allylamine Derivatives in one pot
Peter Atadja - One of the best experts on this subject based on the ideXlab platform.
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aggresome induction by proteasome inhibitor bortezomib and α tubulin hyperacetylation by tubulin deacetylase tdac inhibitor lbh589 are synergistic in myeloma cells
Blood, 2006Co-Authors: Laurence Catley, Peter Atadja, Ellen Weisberg, Tanyel Kiziltepe, Yutzu Tai, Teru Hideshima, Paola Neri, Pierfrancesco Tassone, Dharminder Chauhan, Nikhil C MunshiAbstract:Histone deacetylase (HDAC) inhibitors have shown cytotoxicity as single agents in preclinical studies for multiple myeloma (MM) cells. LBH589 is a novel Hydroxamic Acid Derivative that at low nanomolar concentrations induces apoptosis in MM cells resistant to conventional therapies via caspase activation and poly-(ADP-ribose) polymerase (PARP) cleavage. Significant synergistic cytotoxicity was observed with LBH589 in combination with bortezomib against MM cells that were sensitive and resistant to dexamethasone (Dex), as well as primary patient MM cells. LBH589 at low nanomolar concentrations also induced α-tubulin hyperacetylation. Aggresome formation was observed in the presence of bortezomib, and the combination of LBH589 plus bortezomib induced the formation of abnormal bundles of hyeracetylated α-tubulin but with diminished aggresome size and apoptotic nuclei. These data confirm the potential clinical benefit of combining HDAC inhibitors with proteasome inhibitors, and provide insight into the mechanisms of synergistic anti-MM activity of bortezomib in combination with LBH589.
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targeting tumor angiogenesis with histone deacetylase inhibitors the Hydroxamic Acid Derivative lbh589
Clinical Cancer Research, 2006Co-Authors: David Z Qian, Yukihiko Kato, Shabana Shabbeer, Yongfeng Wei, Hendrik M W Verheul, Brenda Salumbides, Tolib Sanni, Peter Atadja, Roberto PiliAbstract:Purpose: Angiogenesis is required for tumor progression and represents a rational target for therapeutic intervention. Histone deacetylase (HDAC) inhibitors have been shown to have activity against various tumor cell types by inhibiting proliferation and inducing apoptosis both in vitro and in vivo . HDAC inhibitors have also been reported to inhibit angiogenesis. The goal of this study was to characterize the antiangiogenic and antitumor activity of a recently developed HDAC inhibitor, the Hydroxamic Derivative LBH589. Materials and Methods: To evaluate the antiangiogenesis activity of LBH589, we did cell cycle analysis, cell proliferation, tube formation, invasion assays in vitro , and Matrigel plug assay in vivo . To determine the antitumor activity of LBH589, we established human prostate carcinoma cell PC-3 xenografts in vivo . To evaluate the effect of LBH589 on endothelial signaling pathways, gene expression, and protein acetylation, we did Western blots and reverse transcription-PCR in human umbilical vein endothelial cells (HUVEC). Immunohistochemical analysis was done to evaluate new blood vessel formation in vivo . Results: LBH589 induced acetylation of histone H3 and α-tubulin protein in HUVECs. Histone and nonhistone protein acetylation correlated with induction of G 2 -M cell cycle arrest, inhibition of HUVEC proliferation, and viability. Noncytotoxic concentrations of LBH589 inhibited endothelial tube formation, Matrigel invasion, AKT, extracellular signal-regulated kinase 1/2 phosphorylation, and chemokine receptor CXCR4 expression. In vivo dosing of mice with LBH589 (10 mg/kg/d) reduced angiogenesis and PC-3 tumor growth. Conclusion: This study provides evidence that LBH589 induces a wide range of effects on endothelial cells that lead to inhibition of tumor angiogenesis. These results support the role of HDAC inhibitors as a therapeutic strategy to target both the tumor and endothelial compartment and warrant the clinical development of these agents in combination with angiogenesis inhibitors.
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Use of a novel histone deacetylase inhibitor to induce apoptosis in cell lines of acute lymphoblastic leukemia
Haematologica, 2004Co-Authors: Annette Romanski, Peter Atadja, Biserka Bacic, Gesine Bug, Heike Pfeifer, Hilal Gul, Remiszewski Stacy W, Dieter Hoelzer, Martin Ruthardt, Oliver G. OttmannAbstract:BACKGROUND AND OBJECTIVES: Chromatin structure and thereby transcription is controlled by the level of acetylation of histones, which is determined by the balance between histone acetyl transferase (HAT) activity and histone deacetylase (HDAC) activity. HDAC inhibitors are a class of compounds able to regulate gene expression by modulating chromatin structure. There are two major classes of HDAC inhibitors: the Hydroxamic Acid Derivatives such as trichostatin A (TSA) or SAHA, and the butyrates such as phenyl-butyrate. HDAC inhibitors interfere with differentiation, proliferation and apoptosis in tumor cells. Here, we investigated the activity of a new Hydroxamic Acid Derivative, LAQ824, on lymphoblastic cells. DESIGN AND METHODS: Four different pre-B lymphoblastic cell lines: Sup-B15 and TMD-5, both t(9;22) positive, SEM, t(4;11) positive, and NALM-6 cells were exposed to the Hydroxamic Acid Derivatives, LAQ824 and TSA. Histone hyperacetylation, apoptosis, cell cycle and related pathways were assessed by flow cytometry and Western blotting. RESULTS: LAQ824 significantly inhibited the proliferation of leukemic lymphoblastic cell lines. The effect of LAQ824 was due to increased apoptosis accompanied by activation of caspase-3 and caspase-9, cleavage of poly(ADP-ribose)-polymerase (PARP) as well as by down-regulation of Bcl-2 and disruption of the mitochondrial membrane potential. Surprisingly, LAQ824-induced apoptosis was at least partially independent of caspase activation as indicated by the fact that LAQ824-induced apoptosis was inhibited only partially in both t(9;22) positive Sup-B15 and TMD-5 cells, whereas no inhibition was observed in t(4;11) positive SEM cells upon exposure to the polycaspase inhibitor zVAD-fmk. INTERPRETATION AND CONCLUSIONS: Our study establishes that LAQ824 is a promising agent for the therapy of acute lymphoblastic leukemia.
Tarek Aboul-fadl - One of the best experts on this subject based on the ideXlab platform.
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Full Paper Synthesis of 5-Phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3carboxylic Acid Derivatives of Potential Anti-inflammatory Activity
2014Co-Authors: Safwat M. Rabea, Nawal A. El-koussi, Hoda Y. Hassan, Tarek Aboul-fadlAbstract:A series of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid Derivatives 4–10 were synthesized by rearrangement of 4-(3-pyridyl)-hydrazono-2-phenyl-2-oxazolin-5-one 3 in the presence of different nucleophiles to afford Derivatives 4, 7, and 8, while Hydroxamic Acid Derivative 6 was prepared from reaction of methyl ester 4 with hydroxylamine hydrochloride. Semicarbazide 9 and thiosemicarbazide 10, Derivatives of the 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid, were synthesized via hydrazide 8 with potassium cyanate and appropriate isothiocyanate, respectively. The structures of the synthesized compounds were confirmed by elemental analyses, IR, 1 H-NMR, and mass spectra. The results of the anti-inflammatory activity of the synthesized Derivatives showed that most of the tested compounds 4–10 showed significant inhibition against carrageenan-induced rat paw edema in albino rats. Derivatives 4 and 8 showed promising results and were found to be equipotent or more potent than Indomethacin and Celecoxi
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Synthesis of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid Derivatives of potential anti-inflammatory activity.
Arch Pharm, 2006Co-Authors: Safwat M. Rabea, Nawal A. El-koussi, Hoda Y. Hassan, Tarek Aboul-fadlAbstract:A series of 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid Derivatives 4-10 were synthesized by rearrangement of 4-(3-pyridyl)-hydrazono-2-phenyl-2-oxazolin-5-one 3 in the presence of different nucleophiles to afford Derivatives 4, 7, and 8, while Hydroxamic Acid Derivative 6 was prepared from reaction of methyl ester 4 with hydroxylamine hydrochloride. Semicarbazide 9 and thiosemicarbazide 10, Derivatives of the 5-phenyl-1-(3-pyridyl)-1H-1,2,4-triazole-3-carboxylic Acid, were synthesized via hydrazide 8 with potassium cyanate and appropriate isothiocyanate, respectively. The structures of the synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR, and mass spectra. The results of the anti-inflammatory activity of the synthesized Derivatives showed that most of the tested compounds 4-10 showed significant inhibition against carrageenan-induced rat paw edema in albino rats. Derivatives 4 and 8 showed promising results and were found to be equipotent or more potent than Indomethacin and Celecoxib as reference drugs at two dose levels, 5 and 10 mg/kg, and they have no ulcerogenic activity
Fumitaka Shirozu - One of the best experts on this subject based on the ideXlab platform.
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Practical Approach for Asymmetric Hydroxyamination of Aldehydes with in Situ Generated Nitrosocarbonyl Compounds: Application to One-Pot Synthesis of Chiral Allylamines
Organic letters, 2014Co-Authors: Taichi Kano, Fumitaka Shirozu, Keiji MaruokaAbstract:The highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from a Hydroxamic Acid Derivative was realized by simple and readily available chiral amine catalysts. The resulting hydroxyamination products were readily converted to the corresponding chiral 1,2-aminoalcohol or allylamine Derivatives in one pot.
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Practical Approach for Asymmetric Hydroxyamination of Aldehydes with in Situ Generated Nitrosocarbonyl Compounds: Application to One-Pot Synthesis of Chiral Allylamines
2014Co-Authors: Taichi Kano, Fumitaka Shirozu, Keiji MaruokaAbstract:The highly regio- and enantioselective hydroxyamination of aldehydes with in situ generated nitrosocarbonyl compounds from a Hydroxamic Acid Derivative was realized by simple and readily available chiral amine catalysts. The resulting hydroxyamination products were readily converted to the corresponding chiral 1,2-aminoalcohol or allylamine Derivatives in one pot
