References of "Goffin, Eric"
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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 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 detailNew Fluorinated 1,2,4-Benzothiadiazine 1,1-Dioxides: Discovery of an Orally Active Cognitive Enhancer Acting through Potentiation of the 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid Receptors
Francotte, Pierre ULg; Goffin, Eric ULg; Fraikin, Pierre ULg et al

in Journal of Medicinal Chemistry (2010), 53

In the search of a potent cognitive enhancer, a series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as positive allosteric modulators of the AMPA receptors. In ... [more ▼]

In the search of a potent cognitive enhancer, a series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as positive allosteric modulators of the AMPA receptors. In the present work, we focused our efforts on the insertion of mono- or polyfluoro- substituted alkyl chains at the 4-position of the thiadiazine ring in an attempt to enhance the pharmacokinetic behavior of previously described compounds. Among all the described compounds, 7-chloro-4-(2-fluoroethyl)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide, 12b, was shown to exert a strong activity on AMPA receptors in vitro and a marked cognitive-enhancing effect in vivo after oral administration to Wistar rats. Considering its in vivo activity, the metabolic degradation of 12b was studied and compared to that of its nonfluorinated analogue 9b. Taken together, results of this study clearly validated the positive impact of the fluorine atom on the alkyl chain at the 4-position of benzothiadiazine dioxides on activity and metabolic stability. [less ▲]

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See detailDesign, synthesis, and pharmacology of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors
Francotte, Pierre ULg; De Tullio, Pascal ULg; Goffin, Eric ULg et al

in Journal of Medicinal Chemistry (2007), 50(13), 3153-3157

A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the ... [more ▼]

A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the 7-position of the heterocycle. The biological evaluation was achieved by measuring the AMPA current in rat cortex mRNA-injected Xenopus oocytes. The most potent compound, 4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in an object recognition test in rats demonstrating cognition enhancing effects in vivo after oral administration. [less ▲]

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See detailIn Search of Novel Ampa Potentiators
Francotte, Pierre ULg; De Tullio, Pascal ULg; Fraikin, Pierre ULg et al

in Recent Patents on CNS Drug Discovery (2006), 1(3), 239-46

Glutamate is the major excitatory neurotransmitter in the brain. Amongst ionotropic receptors responding to glutamate, the AMPA subtype has been considered as essential for the fast excitatory ... [more ▼]

Glutamate is the major excitatory neurotransmitter in the brain. Amongst ionotropic receptors responding to glutamate, the AMPA subtype has been considered as essential for the fast excitatory neurotransmission in the central nervous system and the expression and maintenance of long-term potentiation. As glutamate is known to be involved in many neurological and psychiatric disorders, AMPA receptors seem to represent interesting targets to develop therapeutic drugs. Hence, the enhancement of AMPA signals is an approach currently investigated for the management of Alzheimer's disease, schizophrenia or mood disorders. In particular, many efforts are being conducted in the development of AMPA positive allosteric modulators ("potentiators"), which alter the rate of receptor desensitization. The major chemical families developed as AMPA potentiators are aniracetam derivatives, cyclothiazide derivatives and biarylpropylsulfonamides derivatives. [less ▲]

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See detailIn vitro screening of some Strychnos species for antiplasmodial activity
Philippe, Geneviève ULg; Angenot, Luc ULg; De Mol, Patrick ULg et al

in Journal of Ethnopharmacology (2005), 97(3), 535-539

The antiplasmodial activity of crude extracts of 19 species of Strychnos (Loganiaceae) was assessed in vitro against a chloroquine-susceptible strain of Plasmodium falciparum. For each species, ethyl ... [more ▼]

The antiplasmodial activity of crude extracts of 19 species of Strychnos (Loganiaceae) was assessed in vitro against a chloroquine-susceptible strain of Plasmodium falciparum. For each species, ethyl acetate (EtOAc) extracts were analysed and, for the most active species, methanolic (MeOH) extracts were also tested. Among them, Strychnos variabilis De Wild. seemed to be very promising (inhibitory concentration 50% (IC50) < 5 microg/ml) whereas two other species, Strychnos gossweileri Exell and Strychnos mellodora S. Moore, could be interesting (IC50 < 15 microg/ml) in further antimalarial studies. [less ▲]

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See detailSupercritical carbon dioxide extraction of tagitinin C from Tithonia diversifolia
Ziemons, Eric ULg; Goffin, Eric ULg; Lejeune, Robert ULg et al

in Journal of Supercritical Fluids (2005), 33(1), 53-59

Different parameters as temperature, pressure, solvent mass and sample granulometry governing the extraction yield of tagitinin C from the aerial parts of Tithonia diversifolia were optimised. An ... [more ▼]

Different parameters as temperature, pressure, solvent mass and sample granulometry governing the extraction yield of tagitinin C from the aerial parts of Tithonia diversifolia were optimised. An experimental design was carried out to map the effects of pressure (at 20.3, 30.4 and 40.5 MPa) and temperature (at 40, 60 and 80degreesC) on the extraction yield of the active component and to determine the optimal conditions for the extraction of tagitinin C from T diversifolia. The best conditions are met for a pressure of 35.0 MPa and a temperature of 68degreesC. The effect of the particle size was studied under low pressure (13.7 MPa) and temperature (40degreesC) conditions, which failed to extract quantitatively the tagitinin C from leaves sieved to 250 mum size. The reduction of the particle size increased the extraction yield which became comparable to that of the optimised SFE for the particle in the range of 0-63 mum. From the analysis of extraction kinetic curves of 200 mg of plant with supercritical carbon dioxide (range of 5-30 g), it appears that 15 g of this supercritical fluid is never limiting. The optimised supercritical fluid extraction (SFE) was compared favourably to Soxhlet extraction with dichloromethane (S) and to maceration followed by lixiviation with diethyl ether (ML), which gave similar extraction yields but higher extract content of tagitinin C were found using SFE (15.6 and 30.7% w/w tagitinin C in S and ML extracts, respectively, versus 52.8% in SFE extract). [less ▲]

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See detailIn vitro and in vivo antimalarial properties of isostrychnopentamine, an indolomonoterpenic alkaloid from Strychnos usambarensis
Frederich, Michel ULg; Tits, Monique ULg; Goffin, Eric ULg et al

in Planta Medica (2004), 70(6), 520-525

Isostrychnopentamine (ISP) is an asymmetric indolomonoterpenic alkaloid isolated from the leaves of Strychnos usambarensis. The in vitro antiplasmodial activities against five Plasmodium falciparum cell ... [more ▼]

Isostrychnopentamine (ISP) is an asymmetric indolomonoterpenic alkaloid isolated from the leaves of Strychnos usambarensis. The in vitro antiplasmodial activities against five Plasmodium falciparum cell lines were evaluated: ISP possessed an in vitro IC (50) near 0.1 microM against all P. falciparum cell lines tested (chloroquine-resistant and chloroquine-sensitive lines) and showed antiplasmodial selectivity compared to cytotoxicity on human cell lines. The stage-dependent susceptibility to a short exposure of ISP was then investigated. The ring stage was shown to be the most sensitive one, but all stages were affected by ISP treatment. By means of fluorescence microscopy, it was shown that ISP was not accumulated inside the food vacuole of the parasite. Finally, the in vivo antimalarial activities against the P. berghei NK173 and P. vinckei petteri murine strains were determined. The ED (50) in vivo was about 30 mg/kg/day by the intraperitoneal route (after 4 days treatment). [less ▲]

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See detailFT-IR measurement of tagitinin C after solvent extraction from Tithonia diversifolia
Ziemons, Eric ULg; Goffin, Eric ULg; Lejeune, Robert ULg et al

in Talanta (2004), 62(2), 383-387

Tagitinin C, an antiplasmodial compound, identified as one major compound of the subtropical medicinal plant, Tithonia diversifolia, was, determined by FT-IR spectroscopy method. The crude ether extracts ... [more ▼]

Tagitinin C, an antiplasmodial compound, identified as one major compound of the subtropical medicinal plant, Tithonia diversifolia, was, determined by FT-IR spectroscopy method. The crude ether extracts from aerial parts of the plant were evaporated to dryness and re-dissolved in tetrachloroethylene (C2Cl4) before analysis. The magnitude of the absorbance of the very specific C=O stretching vibration (v(c=o)) at 1664.8 cm(-1) was exploited in order to quantify tagitinin C. The determination coefficient (r(2)) of the calibration scale was 0.9994, the detection limit was lower than 3 mug ml(-1) and the quantification limit was lower than 10 mug ml(-1). Recovery values from 100.5 to 101.7% were found for spiked concentration levels from 19.91 to 89.95 mug ml(-1). The main characteristics of the curves obtained from the calibration standards and from the standard addition technique were not statistically different (Student t-test) suggesting that matrix effects were negligible. The results obtained for the determination of tagitinin C in the crude ether extract from aerial parts of T diversifolia by LC and FT-IR spectroscopic method agreed well: 0.76 +/- 0.02 and 0.773 +/- 0.009, of tagifinin C in dried plant respectively. (C) 2003 Elsevier B.V. All rights reserved. [less ▲]

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