References of "Masereel, Bernard"
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See detailBM-573 inhibits the development of early atherosclerotic lesions in Apo E deficient mice by blocking TP receptors and thromboxane synthase.
Cherdon, Céline ULg; Rolin, Stephanie; Hanson, Julien ULg et al

in Prostaglandins & Other Lipid Mediators (2011)

Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2() have recently ... [more ▼]

Atherosclerosis is the principal cause of mortality in industrialized countries. Its development is influenced by several mediators of which thromboxane A(2) (TXA(2)) and 8-iso-PGF(2() have recently received a lot of attention. This study aimed to investigate the effect of a dual thromboxane synthase inhibitor and thromboxane receptor antagonist (BM-573) and ASA on lesion formation in apolipoprotein E-deficient mice. The combination of ASA and BM-573 was also studied. Plasma measurements demonstrated that the treatments did not affect body weight or plasma cholesterol levels. BM-573, but not ASA, significantly decreased atherogenic lesions as demonstrated by macroscopic analysis. Both treatments alone inhibited TXB(2) synthesis but only BM-573 and the combination therapy were able to decrease firstly, plasma levels of soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) and secondly, the expression of these proteins in the aortic root of Apo E. These results were confirmed in endothelial cell cultures derived from human saphenous vein endothelial cells (HSVECs). In these cells, BM-573 also prevented the increased mRNA expression of ICAM-1 and VCAM-1 induced by U-46619 and 8-iso-PGF(2(). Our results show that a molecule combining receptor antagonism and thromboxane synthase inhibition is more efficient in delaying atherosclerosis in Apo E(-/-) mice than sole inhibition of TXA(2) formation. [less ▲]

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See detailIndol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors.
Dolusic, Eduard; Larrieu, Pierre; Blanc, Sébastien et al

in Bioorganic & Medicinal Chemistry (2011), 19(4), 1550-61

Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships ... [more ▼]

Indoleamine 2,3-dioxygenase (IDO) is a heme dioxygenase which has been shown to be involved in the pathological immune escape of diseases such as cancer. The synthesis and structure-activity relationships (SAR) of a novel series of IDO inhibitors based on the indol-2-yl ethanone scaffold is described. In vitro and in vivo biological activities have been evaluated, leading to compounds with IC(50) values in the micromolar range in both tests. Introduction of small substituents in the 5- and 6-positions of the indole ring, indole N-methylation and variations of the aromatic side chain are all well tolerated. An iron coordinating group on the linker is a prerequisite for biological activity, thus corroborating the virtual screening results. [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 detailEffects of reperfusion on left ventricular hemodynamics and ventriculo-arterial coupling in acutely ischemic pigs
Lanoye, Lieve; KOLH, Philippe ULg; Rolin, Stéphanie et al

in Computer Methods in Biomechanics & Biomedical Engineering (2005), 8(suppl. 1), 169-170

Rapid restoration of coronary blood flow following a period of myocardial ischemia (due to coronary occlusion) is mandatory to preserve the cardiac muscle. Reperfusion, however, not necessarily restores ... [more ▼]

Rapid restoration of coronary blood flow following a period of myocardial ischemia (due to coronary occlusion) is mandatory to preserve the cardiac muscle. Reperfusion, however, not necessarily restores cardiac function, and cellular damage of the cardiac muscle cells following reperfusion (reperfusion injury) is well documented. The aim of this study was to investigate the effects of reperfusion on left ventricular (LV) hemodynamics and on left ventriculo-arterial (VA) coupling in acutely ischemic pigs. [less ▲]

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See detailCharacterization of an original model of myocardial infarction provoked by coronary artery thrombosis induced by ferric chloride in pig
Dogné, Jean-Michel ULg; Rolin, Stéphanie; Petein, Michel et al

in Thrombosis Research (2005), 116(5), 431-442

Background: Great advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely ... [more ▼]

Background: Great advances have been made in the prevention of thrombotic disorders by developments of new pharmacological and surgical treatments. Animal models of arterial thrombosis have largely contributed to the discovery and to the validation of original treatments. The purpose of the present work was to develop and validate an original model of acute myocardial infarction provoked in pig by thrombosis of the left anterior descending (LAD) coronary artery induced by topical application of ferric chloride solution. Methods and results: Myocardial infarction, resulting from an occlusive and adherent mixed thrombus formed in the LAD coronary artery, was examined at macroscopic level using dual staining technique (Evans blue dye; triphenyltetrazolium chloride) and at microscopic level using conventional histological analyses and immunohistochemical detection of desmin. Biochemical markers (troponin T and ATP), platelet reactivity and standard hemodynamic parameters (such as stroke volume, ejection fraction, stroke work and cardiac output) have also been evaluated. From these analyses, it was demonstrated that each pig developed a transmural area of irreversible damage mainly located in the anteroseptal region of the left ventricle. The more progressive development of coronary artery occlusion, as compared to an abrupt Ligation, was accompanied by a correspondingly progressive impairment in hemodynamics. Conclusion: We conclude that this original porcine model of myocardial infarction is quite close to clinical pathophysiological conditions, such as thrombus formation occurring after atherosclerotic plaque rupture. This certainly constitutes a further argument in favour of this model to assess pharmaceutical or mechanical support of an acutely ischemic heart. (c) 2005 Elsevier Ltd. All rights reserved. [less ▲]

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See detailIn vitro and in vivo pharmacological characterization of BM-613 [N-n-pentyl-N'-[2-(4'-methylphenylamino)-5-nitrobenzenesulfonyl]urea]
Hanson, Julien ULg; Rolin, Stéphanie; Reynaud, Denis et al

in Journal of Pharmacology and Experimental Therapeutics (The) (2005), 313

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See detailPharmacological profile and therapeutic potential of BM-573, a combined thromboxane receptor antagonist and synthase inhibitor.
Ghuysen, Alexandre ULg; Dogné, Jean-Michel; Chiap, Patrice ULg et al

in Cardiovascular Drug Reviews (2005), 23(1), 1-14

BM-573 (N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea), a torsemide derivative, is a novel non-carboxylic dual TXA2 synthase inhibitor and receptor antagonist. The pharmacological ... [more ▼]

BM-573 (N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl]urea), a torsemide derivative, is a novel non-carboxylic dual TXA2 synthase inhibitor and receptor antagonist. The pharmacological profile of the drug is characterized by a higher affinity for the thromboxane receptor than that of SQ-29548, one of the most powerful antagonists described to date, by a complete prevention of human platelet aggregation induced by arachidonic acid at a lower dose than either torsemide or sulotroban, and by a significantly prolonged closure time measured by the platelet function analyser (PFA-100). Moreover, at the concentrations of 1 and 10 microM, BM-573 completely prevented production of TXB2 by human platelets activated by 0.6 mM of arachidonic acid. BM-573 prevents rat fundus contraction induced by U-46619 but not by prostacyclin or other prostaglandins. Despite possessing a chemical structure very similar to that of a diuretic torsemide, BM-573 has no diuretic activity. BM-573 does not prolong bleeding time and, unlike some of the other sulfonylureas, has no effect on blood glucose levels. In vivo, BM-573 appears to have antiplatelet and antithrombotic activities since it reduced thrombus weight and prolonged the time to abdominal aorta occlusion induced by ferric chloride. BM-573 also relaxed rat aorta and guinea pig trachea precontracted with U-46619. In pigs, BM-573 completely antagonized pulmonary hypertensive effects of U-46619 and reduced the early phase of pulmonary hypertension in models of endotoxic shock and pulmonary embolism. Finally, BM-573 protected pigs from myocardial infarction induced by coronary thrombosis. These results suggest that BM-573 should be viewed as a promising therapeutic agent in the treatment of pulmonary hypertension and syndromes associated with platelet activation. [less ▲]

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See detailSynthèse de b-cyclodextrines modifiées
Bertolla, Carine; Piette, Marie ULg; Evrard, Brigitte ULg et al

Poster (2003, May)

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See detailCoumarinic derivatives as mechanism-based inhibitors of alpha-chymotrypsin and human leukocyte elastase
Pochet, Lionel; Doucet, Caroline; Dive, Georges ULg et al

in Bioorganic & Medicinal Chemistry (2000), 8(6), 1489-1501

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See detailLes activateurs de canaux potassiques: étude structurale comparative du pinacidil, du diazoxide et du cromakalim
Dupont, Léon ULg; Pirotte, Bernard ULg; De Tullio, Pascal ULg et al

in Annales Pharmaceutiques Françaises (1995), 53(5), 201-208

A conformational analysis has been performed with SYBYL starting from the energy optimized (Tripos force field) X-ray conformation of (R,S)-pinacidil. The geometry of four selected low energy conformers ... [more ▼]

A conformational analysis has been performed with SYBYL starting from the energy optimized (Tripos force field) X-ray conformation of (R,S)-pinacidil. The geometry of four selected low energy conformers has been reoptimized using the AM1 semiempirical Molecular Orbital method (MOPAC 5.0), and the total energy of the optimized conformers has been compared. In spite of an apparent structural dissimilarity, a good analogy has been found between the calculated isopotential map of diazoxide and that of at least one selected low energy conformer of pinacidil. It has been suggested that, unlike cromakalim, the low but observable activity of pinacidil on pancreatic B-cells could be explained by adoption for this compound of a conformation having a diazoxide-like stereoelectronical imprint which could assume a similar interaction on the same biological receptor. [less ▲]

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See detailSynthèse, étude théorique et évaluation biologique de dérivés du 4-amino-4H-1,2,4-triazole analogues des antibiotiques b-lactamiques
Pirotte, Bernard ULg; Dive, Georges ULg; Delarge, Jacques et al

in European Journal of Medicinal Chemistry (1992), 27(3), 193-205

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