References of "Pirotte, Bernard"
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See detailSynthesis and characterization of Zn(1-x)NixAl2O4 spinels as a new heterogeneous catalyst of Biginelli's reaction
Akika, F.-Z.; Kihal, N.; Habila, T. et al

in Bulletin of the Korean Chemical Society [= BKCS] (2013), 34

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See detailTriphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels
Constant-Urban, C.; Charif, M.; Goffin, Eric ULg et al

in Bioorganic & Medicinal Chemistry Letters (2013), 23

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See detailN-tert-butyl-N'-[5-cyano-2-(4-methylphenoxy)phenylsulfonyl]urea, a new TXA₂ receptor antagonist
Bambi Nyanguile, S.M.; Mangwala Kimpende, P.; Pirotte, Bernard ULg et al

in Acta Crystallographica Section C-Crystal Structure Communications (2013), 69

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See detailEffects of diazoxide, benzothiadiazine and benzopyrane derivatives on mitochondrial proton and electron leaks of cardiomyocytes (H9C2 cell line).
Mouithys-Mickalad, Ange ULg; Ceusters, Justine ULg; Charef, M et al

Poster (2013)

Background: Mitochondria are double membrane- organelles that play a central role in cellular metabolism, calcium homeostasis and redox signaling. They have been also considered as main producers of ... [more ▼]

Background: Mitochondria are double membrane- organelles that play a central role in cellular metabolism, calcium homeostasis and redox signaling. They have been also considered as main producers of adenosine triphosphate (ATP) and reactive oxygen species (ROS). In many cancer cells those organelles become dysfunctional leading to a shift of energy metabolism from oxidative phosphorylation to active glycolysis and an increase of ROS generation. According to Warberg’ theory, cancer damage might occur at the mitochondrial level, affecting tiny structures within each cell implicated in the energy production through ATP. New insight is that mitochondria might be a good therapeutic target for metabolic syndromes, ischemia/reperfusion injury and organs transplantation. Therefore, search for novel molecules able to keep mitochondria functional are of relevant interest. Methodology: Cardiomyocytes (H9C2 cells) were from ATCC (USA) and grown till confluence. The basal cellular respiratory rate, proton and electron leaks as well as ATP production were measured with the High Resolution Oxygraphy (Oroboros, Austria). All compounds: diazoxide (DIAZ), diazoxide –related analogs (1: BPDZ-259, 2: BPDZ-444), and benzopyran derivatives (3: BPDZ-490, 4: BPDZ-711) were tested at final concentration of 10-5 M, except when specified and compared to control samples (cells with or without DMSO). Results and conclusion: The basal respiratory rate of H9C2 cells (5x106/mL) was changed depending on the chemical structure of the tested compounds: e.g. compound 3 strongly enhanced the routine respiration, while 4 displayed a marked lowering effect. In contrast, the addition of similar concentration of benzothiadiazin derivatives (1, 2) had no effect on routine respiration but also on the other respiratory parameters such as oligomycin-induced leak and ATP production. Similar profile was obtained with the reference molecule: diazoxide. Overall, our findings indicate that both diazoxide-like analogues (1 and 2) and diazoxide were without significant effect on basal respiration, ATP production, even on maximal respiration. Interestingly, two derivatives show opposite effects: compound 3 behaves as a uncoupling agent and the other one (4) exhibits a real lowering effect on respiration but that was reversible. The latter effect might be of interest if this kind of molecules could be used for further use as an agent for organ conservation during transplantation. Our results also demonstrate that diazoxide, a well-known Mito-KATP opener, did not exert its effect beside of clinical situation like ischemia/reperfusion injury. [less ▲]

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See detailHeterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A4
Hanson, Julien ULg; Ferreiros, Nerea; Pirotte, Bernard ULg et al

in Biochemical Pharmacology (2013), 85

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See detailAMPA receptor positive allosteric modulators: a patent review
Pirotte, Bernard ULg; Francotte, Pierre ULg; Goffin, Eric ULg et al

in Expert Opinion on Therapeutic Patents (2013), 23

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See detailDevelopment of original 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas as thromboxane A2 receptor antagonists
Bambi Nyanguile, Sylvie-Mireille ULg; Hanson, Julien ULg; Dogné, Jean-Michel et al

Poster (2012, August)

A series of novel 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas were synthesized. The newly synthesized compounds were tested in vitro and ex vivo as thromboxane A2 receptor antagonists. Some of the ... [more ▼]

A series of novel 2-aryloxy/arylamino-5-cyanobenzenesulfonylureas were synthesized. The newly synthesized compounds were tested in vitro and ex vivo as thromboxane A2 receptor antagonists. Some of the test compounds showed potent thromboxane A2 receptor antagonist activity. Three compounds (7h, 8h and 8e) were identified as leads for further pharmacological and toxicological studies. [less ▲]

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See detailTribute to a living legend
Hoekstra, W.J.; Pirotte, Bernard ULg

in Current Medicinal Chemistry (2012), 19

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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 detailThermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2
Krintel, Christian; Frydenvang, Karla; Olsen, Lars et al

in Biochemical Journal (2012), 441

Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer’s disease. These modulators bind within the ... [more ▼]

Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer’s disease. These modulators bind within the dimer interface of the LBD (ligand-binding domain) and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. In the present study, we employ isothermal titration calorimetry to determine binding affinities and thermodynamic details of binding of modulators of GluA2. A mutant of the LBD of GluA2 (LBD-L483Y-N754S) that forms a stable dimer in solution was used. The potent GluA2 modulator BPAM-97 was used as a reference compound. Evidence that BPAM-97 binds in the same pocket as the well-known GluA2 modulator cyclothiazide was obtained from X-ray structures. The LBD-L483Y-N754S:BPAM-97 complex has aKd of 5.6 μM (Δ H = − 4.9 kcal/mol, − T Δ S = − 2.3 kcal/mol; where 1 kcal ≈4.187 kJ). BPAM-97 was used in a displacement assay to determine a Kd of 0.46 mM (Δ H = − 1.2 kcal/mol, − T Δ S = − 3.3 kcal/mol) for the LBD-L483Y-N754S:IDRA-21 complex. The major structural factors increasing the potency of BPAM-97 over IDRA-21 are the increased van der Waals contacts to, primarily, Met496 in GluA2 imposed by the ethyl substituent of BPAM-97. These results add important information on binding affinities and thermodynamic details, and provide a new tool in the development of drugs against cognitive disorders. Key words: binding affinity, crystal structure, ionotropic glutamate receptor, isothermal titration calorimetry, positive allosteric modulator [less ▲]

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