References of "European Journal of Medicinal Chemistry"
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See detailSynthesis, characterization and biological evaluation of benzothiazoles and tetrahydrobenzothiazoles bearing urea or thiourea moieties as vasorelaxants and inhibitors of the insulin releasing process
Harrouche, K; Renard, JF; Bouider, N et al

in European Journal of Medicinal Chemistry (2016), 115

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See detailStructure-activity relationship of hybrids of Cinchona alkaloids and bile acids with in vitro antiplasmodial and antitrypanosomal activities.
Leverrier, Aurelie; Bero, Joanne; Cabrera, Julian et al

in European journal of medicinal chemistry (2015), 100

In this work, a series of hybrid compounds were tested as antiparasitic substances. These hybrids were prepared from bile acids and a series of antiparasitic Cinchona alkaloids by the formation of a ... [more ▼]

In this work, a series of hybrid compounds were tested as antiparasitic substances. These hybrids were prepared from bile acids and a series of antiparasitic Cinchona alkaloids by the formation of a covalent C-C bond via a decarboxylative Barton-Zard reaction between the two entities. The bile acids showed only weak antiparasitic properties, but all the hybrids exhibited high in vitro activities (IC50: 0.48-5.39 muM) against Trypanosoma brucei. These hybrids were more active than their respective parent alkaloids (up to a 135 fold increase in activity), and displayed good selectivity indices. Aditionally, all these compounds inhibited the in vitro growth of a chloroquine-sensitive strain of Plasmodium falciparum (3D7: IC50: 36.1 nM to 8.72 muM), and the most active hybrids had IC50s comparable to that of artemisinin (IC50: 36 nM). Some structure-activity relationships among the group of 48 hybrids are discussed. The increase in antiparasitic activity may be explained by an improvement in bioavailability, since the more lipophilic derivatives showed the lowest IC50s. [less ▲]

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See detailSynthesis and pharmacological evaluation of 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas as novel thromboxane A2 receptor antagonists
Bambi-Nyanguile, Sylvie-Mireille; Hanson, Julien ULg; OOMS, Annie ULg et al

in European Journal of Medicinal Chemistry (2013), 65C

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See detailMacrocyle-embedded b-lactams as novel inhibitors of the Penicillin Binding Protein PBP2a from MRSA
Dive, Georges ULg; Bouillon, Camille; Sliwa, Aline et al

in European Journal of Medicinal Chemistry (2013), 64

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See detail4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) Inhibits Na+/K+-ATPase and Ras Oncogene Activity in Cancer Cells
Lefranc, F; Xu, Z; Burth, P et al

in European Journal of Medicinal Chemistry (2013), 63

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See detailAntiparasitic hybrids of Cinchona alkaloids and bile acids.
Leverrier, Aurelie; Bero, Joanne; Frederich, Michel ULg et al

in European journal of medicinal chemistry (2013), 66

A series of 16 hybrids of Cinchona alkaloids and bile acids (4a-h, 5a-h) was prepared by means of a Barton-Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were ... [more ▼]

A series of 16 hybrids of Cinchona alkaloids and bile acids (4a-h, 5a-h) was prepared by means of a Barton-Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC(5)(0) values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC(5)(0) </= 6 mug/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC(5)(0) values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6-15.7. [less ▲]

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See detailN-Aryl-N'-(chroman-4-yl)ureas and thioureas display in vitro anticancer activity and selectivity on apoptosis-resistant glioblastoma cells: screening, synthesis of simplified derivatives, and structure-activity relationship analysis.
Goffin, Eric ULg; Lamoral-Theys, Delphine; Tajeddine, Nicolas et al

in European Journal of Medicinal Chemistry (2012), 54

A series of chroman derivatives previously reported as potassium channel openers, as well as some newly synthesized simplified structures, were examined for their in vitro effects on the growth of three ... [more ▼]

A series of chroman derivatives previously reported as potassium channel openers, as well as some newly synthesized simplified structures, were examined for their in vitro effects on the growth of three human high-grade glioma cell lines: U373, T98G, and Hs683. Significant in vitro growth inhibitory activity was observed with 2,2-dimethylchroman-type nitro-substituted phenylthioureas, such as compounds 4o and 4p. Interestingly, most tested phenylureas were found to be slightly less active, but more cell selective (normal versus tumor glial cells, such as 3d, 3e, and 3g), thus less toxic, than the corresponding phenylthioureas. No significant differences were observed in terms of chroman-derivative-induced growth inhibitory effects between glioma cells sensitive to pro-apoptotic stimuli (Hs683 glioma cells) and glioma cells associated with various levels of resistance to pro-apoptotic stimuli (U373 and T98G glioma cells), a feature that suggests non-apoptotic-mediated growth inhibition. Flow cytometry analyses confirmed the absence of pro-apoptotic effects for phenylthioureas and phenylureas when analyzed in U373 glioma cells and demonstrated U373 cell cycle arrest in the G0/G1 phase. Computer-assisted phase-contrast videomicroscopy revealed that 3d and 3g displayed cytostatic effects, while 3e displayed cytotoxic ones. As a result, this work identified phenylurea-type 2,2-dimethylchromans as a new class of antitumor agents to be further explored for an innovative therapeutic approach for high-grade glioma and/or for a possible new mechanism of action. [less ▲]

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See detailSynthesis, crystal structures and electronic properties of isomers of chloro-pyridinylvinyl-1H-indoles.
Moineaux, Laurence; Laurent, Sophie; Reniers, Jeremy et al

in European journal of medicinal chemistry (2012), 54

Three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and tested as inhibitors of human tryptophan 2,3-dioxygenase (hTDO). The crystal structures of two of them were solved by X-ray ... [more ▼]

Three isomers of chloro-3-(2-pyridin-3-ylvinyl)-1H-indole were synthesized and tested as inhibitors of human tryptophan 2,3-dioxygenase (hTDO). The crystal structures of two of them were solved by X-ray diffraction. The solubility of the molecules also was determined experimentally. The molecular electrostatic potentials and dipole moments of the three isomers were calculated by ab initio quantum mechanics (HF/6-311G). The single crystal X-ray analyses reveal non-planar structures. This non-coplanarity is retained during docking of the compounds into a model of hTDO, the molecular target of this series. The position of the Cl atom does not significantly affect the electronic delocalization. Nevertheless, the position of the Cl atom produces a local variation of bond lengths inducing different dipole moments for these isomers. Variations in dipole moments are consistent with the different melting points and crystal packings. Differences in aqueous solubilities are best explained by subtle changes in H-bonds resulting from different accessibilities of the indole NH's due to steric effects of the Cl substituent. The non-coplanarity plays an important role in the crystalline packing of the molecules in contrast to the position of the Cl. This study leads to a better understanding of the structural and electronic characteristics of this chemical series and can potentially help to better understand their inhibitory activity. [less ▲]

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See detailDiscovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors.
Dolusic, Eduard; Larrieu, Pierre; Blanc, Sebastien et al

in European journal of medicinal chemistry (2011), 46(7), 3058-65

Indoleamine 2,3-dioxygenase (IDO) is an important new therapeutic target for the treatment of cancer. With the aim of discovering novel IDO inhibitors, a virtual screen was undertaken and led to the ... [more ▼]

Indoleamine 2,3-dioxygenase (IDO) is an important new therapeutic target for the treatment of cancer. With the aim of discovering novel IDO inhibitors, a virtual screen was undertaken and led to the discovery of the keto-indole derivative 1a endowed with an inhibitory potency in the micromolar range. Detailed kinetics were performed and revealed an uncompetitive inhibition profile. Preliminary SARs were drawn in this series and corroborated the putative binding orientation as suggested by docking. [less ▲]

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See detailSecond-generation sulfonamide inhibitors of D-glutamic acid-adding enzyme: activity optimisation with conformationally rigid analogues of D-glutamic acid.
Sosic, Izidor; Barreteau, Helene; Simcic, Mihael et al

in European journal of medicinal chemistry (2011), 46(7), 2880-94

D-Glutamic acid-adding enzyme (MurD) catalyses the essential addition of d-glutamic acid to the cytoplasmic peptidoglycan precursor UDP-N-acetylmuramoyl-l-alanine, and as such it represents an important ... [more ▼]

D-Glutamic acid-adding enzyme (MurD) catalyses the essential addition of d-glutamic acid to the cytoplasmic peptidoglycan precursor UDP-N-acetylmuramoyl-l-alanine, and as such it represents an important antibacterial drug-discovery target enzyme. Based on a series of naphthalene-N-sulfonyl-d-Glu derivatives synthesised recently, we synthesised two series of new, optimised sulfonamide inhibitors of MurD that incorporate rigidified mimetics of d-Glu. The compounds that contained either constrained d-Glu or related rigid d-Glu mimetics showed significantly better inhibitory activities than the parent compounds, thereby confirming the advantage of molecular rigidisation in the design of MurD inhibitors. The binding modes of the best inhibitors were examined with high-resolution NMR spectroscopy and X-ray crystallography. We have solved a new crystal structure of the complex of MurD with an inhibitor bearing a 4-aminocyclohexane-1,3-dicarboxyl moiety. These data provide an additional step towards the development of sulfonamide inhibitors with potential antibacterial activities. [less ▲]

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See detailBis-tetrahydroisoquinoline derivatives: Structure analysis of the three stereoisomers of 1,1'-(propane-1,3-diyl)-bis-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline)
Wouters, Johan; Elasaad, Kossay; Norberg, Bernadette et al

in European Journal of Medicinal Chemistry (2010), 45

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See detailLarge ring 1,3-bridged 2-azetidinones: experimental and theoretical studies
Urbach, Allan; Dive, Georges ULg; Tinant, Bernard et al

in European Journal of Medicinal Chemistry (2009), 44

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See detailUnusual cellular uptake of cytotoxic 4-hydroxymethyl-3-aminoacridine.
Peixoto, Paul ULg; Zeghida, Walid; Carrez, Daniele et al

in European journal of medicinal chemistry (2009), 44(11), 4758-63

Aminoacridine derivatives display interesting chemical and biological properties in the field of antitumor agents. The synthesis of 4-hydroxymethyl-3-aminoacridine and its iodo labelled analogue allows ... [more ▼]

Aminoacridine derivatives display interesting chemical and biological properties in the field of antitumor agents. The synthesis of 4-hydroxymethyl-3-aminoacridine and its iodo labelled analogue allows the study of cell distribution using two innovative, complementary and powerful techniques, real time fluorescence microscopy and dynamic secondary ion mass spectrometry (SIMS). All the data point to lysosomal localization of the active molecule. [less ▲]

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See detail6-Substituted 2-Oxo-2h-1-Benzopyran-3-Carboxylic Acid Derivatives in a New Approach of the Treatment of Cancer Cell Invasion and Metastasis
Kempen, I.; Hemmer, Marc ULg; Counerotte, Stéphane ULg et al

in European Journal of Medicinal Chemistry (2008), 43(12), 2735-50

Novel 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives were synthesized and their potency in reducing the invasive behaviour of HT 1080 fibrosarcoma cells was evaluated. Structure ... [more ▼]

Novel 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives were synthesized and their potency in reducing the invasive behaviour of HT 1080 fibrosarcoma cells was evaluated. Structure-activity relationships were deduced from biological results and will be used in further design of new active compounds. In particular, the acetoxymethyl substituent found at the 6-position of previously described active compounds can be replaced by an acetamidomethyl substituent without loss of potency; while the presence of an aryl ester function at the 3-position was preferred to a thioester or an amide function to induce marked biological activity. This work confirms the interest of aryl esters of 6-substituted coumarin-3-carboxylic acids as potential new anti-cancer agents. [less ▲]

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See detailHomology modeling of MT(1) and MT(2) receptors
Farce, Amaury; Chugunov, Anton O.; Logé, Cédric et al

in European Journal of Medicinal Chemistry (2008), 43

Melatonin is a neurohormone synthesized and secreted mainly during the dark period of the circadian cycle by the pineal gland. It has already been proved to be involved in a number of chronobiological ... [more ▼]

Melatonin is a neurohormone synthesized and secreted mainly during the dark period of the circadian cycle by the pineal gland. It has already been proved to be involved in a number of chronobiological processes, most of them being mediated by its membranar receptors MT1 and MT2. Both are members of the GPCR class and, despite the interest they elicit, their 3D structure is still to be described. Models for both human MT1 and MT2 receptors have been constructed by homology modeling, using the X-ray structure of bovine rhodopsin as template. These models have been evaluated in terms of hydrophobic properties of the helices and refined to take into account the rearrangement of GPCRs necessary for their activation, thus leading to a putative activated model for each subtype. [less ▲]

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See detailStructure-based pharmacophore of COX-2 selective inhibitors and identification of original lead compounds from 3D database searching method
Michaux, C.; De Leval, X.; Julémont, F. et al

in European Journal of Medicinal Chemistry (2006), 41

Detailed reference viewed: 36 (0 ULg)