1,4,2-Benzo/pyridodithiazine 1,1-Dioxides Structurally Related to the ATP-Sensitive Potassium Channel Openers 1,2,4-Benzo/pyridothiadiazine 1,1-Dioxides Exert a Myorelaxant Activity Linked to a Distinct Mechanism of Action

in Journal of Medicinal Chemistry (2013), 56

Design, Synthesis and Biological Evaluation of 4-Cycloalkyl-Substituted 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides Acting as AMPA Potentiators

Poster (2012, September)

N-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.

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 ▲]

Development of cognitive enhancers acting through AMPA potentiation: design of novel thienothiadiazine 1,1-dioxides

Poster (2010, September 08)

Ring-fused thiadiazines as core structures for the development of potent AMPA receptor potentiators

in Current Medicinal Chemistry (2010), 17

Design, synthesis and pharmacological evaluation of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides acting as AMPA potentiators

Poster (2008, May 17)

Design, synthèse et évaluation pharmacologique de 1,2,4-thiénothiadiazine 1,1-dioxydes en tant que nouveaux potentialisateurs AMPA

Poster (2007, May)

Design, synthesis and pharmacological evaluation of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides acting as AMPA potentiators

Poster (2006, August)

In Search of Novel Ampa Potentiators

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 ▲]

Supercritical carbon dioxide extraction of tagitinin C from Tithonia diversifolia

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 ▲]