Vassiliki Theodorou - Academia.edu (original) (raw)
Papers by Vassiliki Theodorou
Imatinib mesylate is the leading compound to treat chronic myeloid leukemia (CML) and other cance... more Imatinib mesylate is the leading compound to treat chronic myeloid leukemia (CML) and other cancers, through its inhibition of Bcr-Abl tyrosine kinases. However, resistance to imatinib develops frequently, particularly in late-stage disease and has necessitated the development of new Bcr-Abl inhibitors. The synthesis of a new series of phenylaminopyrimidines, structurally related to imatinib, showed large interest since the introduction of nilotinib. Here, we compare the protein levels in K562 cells treated with either imatinib or with novel imatinib derivates. Our results revealed that among the 986 quantified proteins, 35 had significantly altered levels of expression by imatinib or its derivates. In a second series of experiments, we directly compared the proteomes of imatinib treated K562 cells with those K562 cells treated with any of the four imatinib derivates. More than 1029 protein were quantified, 80 of which had altered levels of expression. Both experiments pointed to changes in the expression of the ATP-dependent RNA helicase DDX3X and of two mitochondrial coiled-coil-helix-coiled-coil-helix domain-containing proteins.
RSC Advances, 2016
We revisited the classical synthetic procedure for imatinib synthesis providing an improved and o... more We revisited the classical synthetic procedure for imatinib synthesis providing an improved and optimized approach in the preparation of a series of new imatinib analogues.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Helvetica Chimica Acta, 2015
First time, new calixarene-based dendrimers, containing calix[4]arene as the core and different g... more First time, new calixarene-based dendrimers, containing calix[4]arene as the core and different generations of Frechet-type poly(benzyl ether) dendrons as building blocks, which possess either Br-atoms or COOtBu groups at their surface, are synthesized and presented.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 2, 2015
Factor-inhibiting hypoxia-inducible factor (HIF)-1 (FIH-1) is an asparaginyl β-hydroxylase enzyme... more Factor-inhibiting hypoxia-inducible factor (HIF)-1 (FIH-1) is an asparaginyl β-hydroxylase enzyme that was initially found to hydroxylate the HIF-α, preventing its transcriptional activity and leading to adaptive responses to hypoxia. More recently, other substrates, such as neurogenic locus notch homolog (Notch), have been found to be alternative FIH targets, but the biologic relevance of this regulation was never investigated. Given the key function of Notch in angiogenesis, we here investigate the role of FIH/Notch signaling in endothelial cells. We report that FIH-1 silencing in HUVECs results in reduced growth and increased apoptosis. The knockdown of FIH is associated with increased Notch2 activity, leading to enhanced expression of the Notch target hairy/enhancer-of-split related with YRPW motif protein 1 (Hey-1). Consistent with recent findings showing that Notch2 suppresses survivin (a key inhibitor of apoptosis), FIH targeting in HUVEC leads to selective repression of surv...
Tetrahedron Letters, 2009
The ability of a series of crown ether-functionalized dendrimers to function as alkali metal picr... more The ability of a series of crown ether-functionalized dendrimers to function as alkali metal picrate extraction agents is assessed by liquid-liquid extraction and 1 H NMR titration experiments. Crown ether-functionalized dendrimers that contain Fréchet-type poly(benzyl ether) dendrons of different generation as building blocks display different extraction characteristics toward alkali metal cations. Positive and negative dendritic effects depending on the generation of the dendrimer are assigned in the complexation behaviour of the dendritic host compounds.
Tetrahedron, 2011
Unsaturated acids, through their acid chlorides, react with tritylamine in the presence of trieth... more Unsaturated acids, through their acid chlorides, react with tritylamine in the presence of triethylamine under mild conditions, to afford in high yield and high regioselectivity the corresponding b,g-unsaturated tritylamides. Detritylation with TFA generates quantitatively b,g-unsaturated primary amides. An investigation of this deconjugative isomerization was performed.
Tetrahedron Letters, 2001
In this work we describe, for the first time, a rapid and efficient method for 17 O selective lab... more In this work we describe, for the first time, a rapid and efficient method for 17 O selective labeling on the b-carboxyl group of an aspartic acid residue already incorporated into a peptide sequence anchored on a solid-phase support. The b-O-benzyl ester of the Asp residue of the Ac-RGD-benzydrylamine resin was successfully saponified using Na 17 OH in a methanol/ dichloromethane mixture. The 17 O selective enriched peptide was then released from the solid support by acidic cleavage. The 17 O NMR spectrum confirmed the 17 O labeling of the Asp b-carboxylate.
Tetrahedron Letters, 2007
ABSTRACT
Tetrahedron Letters, 2004
The hypothesis and the conclusions of previous 17 O NMR studies on the detection of both oxygens ... more The hypothesis and the conclusions of previous 17 O NMR studies on the detection of both oxygens of the carboxylic group of Boc-[ 17 O]Tyr(2,6-diClBzl)-OH in DMSO-d 6 solution (V. Tsikaris et al., Tetrahedron Lett. 2000, 41, 8651) are reconsidered. The appearance of two discrete resonances at 340 and 175 ppm of this protected amino acid is not now attributed: (a) to the reduction of the intramolecular conformational exchange rate, due to the effect of intramolecular hydrogen bonding of the hydroxy part of the carboxyl with the carbonyl oxygen of the Boc-group, and (b) to the effect of solvent viscosity, suggested in the mentioned study. The cause of this phenomenon is now attributed to a strong hydrogen bonding of the polar proton acceptor solvent DMSO with the carboxy group, which effectively reduces the proton exchange rate, thus becoming slow on the 17 O NMR time scale. Ó 2004 Elsevier Ltd. All rights reserved. 17 O NMR spectroscopy provides a powerful and sensitive tool for studying intra-and intermolecular hydrogen bonding effects both in solution and in the solid state. 1-4 Since the oxygen atom is one of the most important atoms constituting hydrogen-bonding structures, 17 O NMR might provide novel and complementary information not readily available from other methods.
Synthesis, 1993
The reaction of the lactols 1a-1d, with malonic acid in hot dimethyl sulfoxide, in the presence o... more The reaction of the lactols 1a-1d, with malonic acid in hot dimethyl sulfoxide, in the presence of piperidinium acetate as catalyst, gives the corresponding (tetrahydrofuran-2-yl)acetic acids 2a, c and (tetrahydropyran-2-yl)acetic acids 2b, d in high yield (65-75%). While the synthesis of the (6-methyltetrahydropyran-2-yl)acetic acid (2d) is highly stereoselective (cis/trans ratio 20:1), no stereoselection was observed with the (5-methyltetrahydrofuran-2-yl)acetic acid (2c) (cis/trans ratio 1:1). This reaction was applied for the synthesis of natural (+)-(S,S)-cis-6-methyltetrahydropyran-2-yl)acetic acid (7), minor constituent of the glandular secretion of the civet cat
Supramolecular Chemistry, 2007
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2006
The simple triarylmethanol hosts, 2 and 4, and their silicon analogues, 1 and 3, have been studie... more The simple triarylmethanol hosts, 2 and 4, and their silicon analogues, 1 and 3, have been studied for comparison of the formation of crystalline inclusion compounds. Clathrate formation experiments showed that replacement of the carbinol C atoms in 2 and 4 by Si atoms to give 1 and 3 resulted in a distinct increase of the capability to form inclusion compounds with organic guests, in particular with alcohols. Moreover, the naphthyl derivatives are much more efficient than the phenyl species, irrespective of the carbinol and silanol features. In order to investigate and compare the guest recognition modes and packing relations of hosts 1-4 in their crystalline inclusion compounds, 11 selected co-crystals, namely
Crystal Growth & Design, 2010
The X-ray crystallographic structures of four new inclusion compounds of the versatile clathrate ... more The X-ray crystallographic structures of four new inclusion compounds of the versatile clathrate host 2,2 0-bis(9hydroxy-9-fluorenyl)biphenyl (1) as well as the crystal structure of the unsolvated host are reported and comparatively discussed with regard to the molecular conformation and the modes of interactions the molecules make use of in the crystal packing. While the inclusion crystals demonstrate full saturation of the hydrogen bond capacity of the host molecule, 1 is only involved in weak intermolecular π-contacts in the solvent-free structure. We draw the conclusion that the well-tried strategy of coordinatoclathration, underlying the present inclusion compounds, should not be regarded as a strict rule with reference to the formation of inclusion crystals but a helpful framework in the search of new efficient clathrate hosts.
Crystal Growth & Design, 2013
ABSTRACT
Crystal Growth & Design, 2011
Imatinib mesylate is the leading compound to treat chronic myeloid leukemia (CML) and other cance... more Imatinib mesylate is the leading compound to treat chronic myeloid leukemia (CML) and other cancers, through its inhibition of Bcr-Abl tyrosine kinases. However, resistance to imatinib develops frequently, particularly in late-stage disease and has necessitated the development of new Bcr-Abl inhibitors. The synthesis of a new series of phenylaminopyrimidines, structurally related to imatinib, showed large interest since the introduction of nilotinib. Here, we compare the protein levels in K562 cells treated with either imatinib or with novel imatinib derivates. Our results revealed that among the 986 quantified proteins, 35 had significantly altered levels of expression by imatinib or its derivates. In a second series of experiments, we directly compared the proteomes of imatinib treated K562 cells with those K562 cells treated with any of the four imatinib derivates. More than 1029 protein were quantified, 80 of which had altered levels of expression. Both experiments pointed to changes in the expression of the ATP-dependent RNA helicase DDX3X and of two mitochondrial coiled-coil-helix-coiled-coil-helix domain-containing proteins.
RSC Advances, 2016
We revisited the classical synthetic procedure for imatinib synthesis providing an improved and o... more We revisited the classical synthetic procedure for imatinib synthesis providing an improved and optimized approach in the preparation of a series of new imatinib analogues.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
An entry from the Cambridge Structural Database, the world's repository for small molecule cr... more An entry from the Cambridge Structural Database, the world's repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
Helvetica Chimica Acta, 2015
First time, new calixarene-based dendrimers, containing calix[4]arene as the core and different g... more First time, new calixarene-based dendrimers, containing calix[4]arene as the core and different generations of Frechet-type poly(benzyl ether) dendrons as building blocks, which possess either Br-atoms or COOtBu groups at their surface, are synthesized and presented.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jan 2, 2015
Factor-inhibiting hypoxia-inducible factor (HIF)-1 (FIH-1) is an asparaginyl β-hydroxylase enzyme... more Factor-inhibiting hypoxia-inducible factor (HIF)-1 (FIH-1) is an asparaginyl β-hydroxylase enzyme that was initially found to hydroxylate the HIF-α, preventing its transcriptional activity and leading to adaptive responses to hypoxia. More recently, other substrates, such as neurogenic locus notch homolog (Notch), have been found to be alternative FIH targets, but the biologic relevance of this regulation was never investigated. Given the key function of Notch in angiogenesis, we here investigate the role of FIH/Notch signaling in endothelial cells. We report that FIH-1 silencing in HUVECs results in reduced growth and increased apoptosis. The knockdown of FIH is associated with increased Notch2 activity, leading to enhanced expression of the Notch target hairy/enhancer-of-split related with YRPW motif protein 1 (Hey-1). Consistent with recent findings showing that Notch2 suppresses survivin (a key inhibitor of apoptosis), FIH targeting in HUVEC leads to selective repression of surv...
Tetrahedron Letters, 2009
The ability of a series of crown ether-functionalized dendrimers to function as alkali metal picr... more The ability of a series of crown ether-functionalized dendrimers to function as alkali metal picrate extraction agents is assessed by liquid-liquid extraction and 1 H NMR titration experiments. Crown ether-functionalized dendrimers that contain Fréchet-type poly(benzyl ether) dendrons of different generation as building blocks display different extraction characteristics toward alkali metal cations. Positive and negative dendritic effects depending on the generation of the dendrimer are assigned in the complexation behaviour of the dendritic host compounds.
Tetrahedron, 2011
Unsaturated acids, through their acid chlorides, react with tritylamine in the presence of trieth... more Unsaturated acids, through their acid chlorides, react with tritylamine in the presence of triethylamine under mild conditions, to afford in high yield and high regioselectivity the corresponding b,g-unsaturated tritylamides. Detritylation with TFA generates quantitatively b,g-unsaturated primary amides. An investigation of this deconjugative isomerization was performed.
Tetrahedron Letters, 2001
In this work we describe, for the first time, a rapid and efficient method for 17 O selective lab... more In this work we describe, for the first time, a rapid and efficient method for 17 O selective labeling on the b-carboxyl group of an aspartic acid residue already incorporated into a peptide sequence anchored on a solid-phase support. The b-O-benzyl ester of the Asp residue of the Ac-RGD-benzydrylamine resin was successfully saponified using Na 17 OH in a methanol/ dichloromethane mixture. The 17 O selective enriched peptide was then released from the solid support by acidic cleavage. The 17 O NMR spectrum confirmed the 17 O labeling of the Asp b-carboxylate.
Tetrahedron Letters, 2007
ABSTRACT
Tetrahedron Letters, 2004
The hypothesis and the conclusions of previous 17 O NMR studies on the detection of both oxygens ... more The hypothesis and the conclusions of previous 17 O NMR studies on the detection of both oxygens of the carboxylic group of Boc-[ 17 O]Tyr(2,6-diClBzl)-OH in DMSO-d 6 solution (V. Tsikaris et al., Tetrahedron Lett. 2000, 41, 8651) are reconsidered. The appearance of two discrete resonances at 340 and 175 ppm of this protected amino acid is not now attributed: (a) to the reduction of the intramolecular conformational exchange rate, due to the effect of intramolecular hydrogen bonding of the hydroxy part of the carboxyl with the carbonyl oxygen of the Boc-group, and (b) to the effect of solvent viscosity, suggested in the mentioned study. The cause of this phenomenon is now attributed to a strong hydrogen bonding of the polar proton acceptor solvent DMSO with the carboxy group, which effectively reduces the proton exchange rate, thus becoming slow on the 17 O NMR time scale. Ó 2004 Elsevier Ltd. All rights reserved. 17 O NMR spectroscopy provides a powerful and sensitive tool for studying intra-and intermolecular hydrogen bonding effects both in solution and in the solid state. 1-4 Since the oxygen atom is one of the most important atoms constituting hydrogen-bonding structures, 17 O NMR might provide novel and complementary information not readily available from other methods.
Synthesis, 1993
The reaction of the lactols 1a-1d, with malonic acid in hot dimethyl sulfoxide, in the presence o... more The reaction of the lactols 1a-1d, with malonic acid in hot dimethyl sulfoxide, in the presence of piperidinium acetate as catalyst, gives the corresponding (tetrahydrofuran-2-yl)acetic acids 2a, c and (tetrahydropyran-2-yl)acetic acids 2b, d in high yield (65-75%). While the synthesis of the (6-methyltetrahydropyran-2-yl)acetic acid (2d) is highly stereoselective (cis/trans ratio 20:1), no stereoselection was observed with the (5-methyltetrahydrofuran-2-yl)acetic acid (2c) (cis/trans ratio 1:1). This reaction was applied for the synthesis of natural (+)-(S,S)-cis-6-methyltetrahydropyran-2-yl)acetic acid (7), minor constituent of the glandular secretion of the civet cat
Supramolecular Chemistry, 2007
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Journal of Inclusion Phenomena and Macrocyclic Chemistry, 2006
The simple triarylmethanol hosts, 2 and 4, and their silicon analogues, 1 and 3, have been studie... more The simple triarylmethanol hosts, 2 and 4, and their silicon analogues, 1 and 3, have been studied for comparison of the formation of crystalline inclusion compounds. Clathrate formation experiments showed that replacement of the carbinol C atoms in 2 and 4 by Si atoms to give 1 and 3 resulted in a distinct increase of the capability to form inclusion compounds with organic guests, in particular with alcohols. Moreover, the naphthyl derivatives are much more efficient than the phenyl species, irrespective of the carbinol and silanol features. In order to investigate and compare the guest recognition modes and packing relations of hosts 1-4 in their crystalline inclusion compounds, 11 selected co-crystals, namely
Crystal Growth & Design, 2010
The X-ray crystallographic structures of four new inclusion compounds of the versatile clathrate ... more The X-ray crystallographic structures of four new inclusion compounds of the versatile clathrate host 2,2 0-bis(9hydroxy-9-fluorenyl)biphenyl (1) as well as the crystal structure of the unsolvated host are reported and comparatively discussed with regard to the molecular conformation and the modes of interactions the molecules make use of in the crystal packing. While the inclusion crystals demonstrate full saturation of the hydrogen bond capacity of the host molecule, 1 is only involved in weak intermolecular π-contacts in the solvent-free structure. We draw the conclusion that the well-tried strategy of coordinatoclathration, underlying the present inclusion compounds, should not be regarded as a strict rule with reference to the formation of inclusion crystals but a helpful framework in the search of new efficient clathrate hosts.
Crystal Growth & Design, 2013
ABSTRACT
Crystal Growth & Design, 2011