(N-pyridinyl)alkanesulfonamides as potent anti-inflammatory drugs

Poster (2008, May)

Development of cognitive enhancers acting through AMPA potentiation: design of novel benzothiadiazine 1,1-dioxides with improved pharmacokinetic profile

Conference (2008, May)

Inhibitory effect of curcuminoids and tetrahydrocurcuminoids on equine activated neutrophils and myeloperoxidase activity

in Physiological Research (2008), 57

KATP channel openers: tissue selectivity of original 3-alkylaminopyrido- and 3-alkylaminobenzothiadiazine 1,1 -dioxides

in Biochemical Pharmacology (2008), 75

Synthesis and pharmacological evaluation of a second generation of pyridothiadiazine 1,1-dioxides acting as AMPA potentiators.

in Bioorganic & Medicinal Chemistry (2008), 16(23), 9948-56

Taking into account structure-activity relationships obtained with our previous series, new diversely substituted 1,2,4-pyridothiadiazine 1,1-dioxides were designed to obtain novel AMPA potentiators. The ... [more ▼]

Taking into account structure-activity relationships obtained with our previous series, new diversely substituted 1,2,4-pyridothiadiazine 1,1-dioxides were designed to obtain novel AMPA potentiators. The aim of this work was focused on the improvement of lipophilicity, which is well known as a critical parameter to obtain in vivo active central nervous system agents. For this purpose, two positions on the pyridine ring were privileged to insert selected groups. Among the synthesized compounds emerged 7-chloro-4-ethyl-3,4-dihydro-2H-pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide (12d), which was evaluated in two memory tests in Wistar rats and showed cognition enhancing effects after intraperitoneal injection at doses as low as 0.3mg/kg. [less ▲]

New pyridinic analogues of nimesulide as potent COXs inhibitors.

Poster (2008)

Design, synthesis, and pharmacological evaluation of cromakalim analogues as pancreatic β-cell-selective KATP channel openers

Conference (2007, October)

Design, synthesis and anticancer activity of novel hydroxylated coumarin derivatives

Conference (2007, October)

Inhibitory Effect of Curcuminoids and Tetrahydrocurcuminoids on Equine Activated Neutrophils and Myeloperoxidase Activity

in Physiological Research (2007), 57(4), 577-587

In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen ... [more ▼]

In the horse, the inflammation response to various pathologies (intestinal strangulations, laminitis, etc.) involves an excessive stimulation of the polymorphonuclear neutrophils releasing reactive oxygen species (ROS) and myeloperoxidase (MPO). The aim of the present work was to study the effect of natural polyphenols, curcuminoids and tetrahydrocurcuminoids (THC) on isolated stimulated equine neutrophils and on the activity of purified MPO. The ROS production and the release of MPO by activated neutrophils were measured by chemiluminescence and ELISA techniques, respectively. The activity of purified MPO was measured by studying its nitration, chlorination or oxidation capacity and by using an original method called SIEFED allowing the study of drug interaction with the enzyme without interferences of the medium. Curcuminoids and THC had dose-dependent inhibitory effects on ROS production and MPO release by activated neutrophils and on purified MPO activity. We suggest that the higher efficacy of curcuminoids versus THC could be explained, at least partially, by its chemical structure: the conjugated double bounds and the plane structure of curcuminoids made easier the neutralization of the radical species generated by activated neutrophils and the interaction of the drug with the active site of MPO. These inhibitory effects of curcuminoids on the oxidant activity of equine neutrophils and on MPO activity open therapeutic perspectives in equine pathologies with excessive inflammatory reactions. [less ▲]

Thrombin activity profile : a powerful ex vivo screening test for the development of anticoagulant drugs

Poster (2007, July)