RESUMEN
Chalcones are an important class of natural compounds that exhibit numerous biological activities. In this paper, we report the synthesis and characterization of new fluorinated chalcone (FCH). The molecular geometry was determined by means of single crystal X-ray diffraction, and density functional theory (DFT) at B3LYP, M06-2X functionals and MP2 method, with the 6-311++G(d,p) basis set, was applied to optimize the ground state geometry and to study the molecular conformational stability. The molecular electrostatic potential (MEP) was also investigated at the same level of theory in order to identify and quantify the possible reactive sites. The FCH crystallizes in the centrossymmetric space group [Formula: see text] with two independent conformers (α and ß) in the asymmetric unit cell. The α conformer is arranged in planar layer whereas the ß creates a layer of non-classical dimer along c axis, that differ from α in about 11° in the orientation of phenyl groups. The stabilization of the ß conformer is achieved by C-H···π arrangement. The small energy difference between the conformers (0.086 kcal mol-1) and the absence of activation energy indicates that the conversion between them can takes place at room temperature and the ß isomer is stable only in solid state. The FCH most electrophilic site occurs on the oxygen atom from the carboxyl group with absolute MEP value of about -52 kcal mol-1 whereas the MEP value calculated for F site is about -23 kcal mol-1.
RESUMEN
Inflammatory diseases and pain are among the main problems that significantly influence the lifestyle of millions of people and existing therapies are not always effective and can cause several adverse effects. In this context, the molecular modifications or synthesis of compounds continue being the best strategies for the identification of new compounds for the treatment of pain and inflammation. The aim of this study was to evaluate the analgesic and anti-inflammatory activities of new analogues of pyrazole compounds containing subunits N-phenyl-1-H-pirazoles and 1,3,4-oxadiazole-2(3H)-thione, LQFM-146, LQFM-147 and LQFM-148. In the acetic acid-induced abdominal writhing test, treatments with LQFM-146, LQFM-147 or LQFM-148 at doses 89, 178 and 356µmol/kg p.o. reduced the abdominal writhing in a dose-dependent manner. In the formalin test, these compounds at dose 178µmol/kg p.o. reduced the licking time only in inflammatory phase of this test, suggesting an antinociceptive effect dependent of the anti-inflammatory effect. The treatment with the three compounds in intermediate dose (178µmol/kg p.o.) reduced the edema at all tested time points in the carrageenan-induced paw edema test and reduced polymorphonuclears cell migration, activity myeloperoxidase and TNF-α levels in the carrageenan-induced pleurisy test. Our date suggest that the new compounds LQFM-146, LQFM-147 and LQFM-148 possess satisfactory anti-inflammatory and antinociceptive effects that involves the reduction of pro-inflammatory cytokines and inhibition of the myeloperoxidase enzyme.