Conception, synthèse et évaluation biologique de nouvelles classes de ligands sérotoninergiques 5-HT7

Parmi tous les neurotransmetteurs identifiés à ce jour, la sérotonine (5-hydroxytryptamine, 5-HT) est impliquée dans le système le plus complexe de récepteurs. Parmi eux, les récepteurs 5-HT7 qui sont les derniers découverts (1993) semblent avoir des implications multiples tant au niveau central que périphérique. Le potentiel thérapeutique représenté par la découverte de ligands 5-HT7 sélectifs vis-à-vis d autres RCPGs a motivé notre projet de recherche. Nos études sont orientées vers la conception de trois classes distinctes de ligands. Une première famille à été conçue sur une charpente benzimidazolone. Diverses pharmacomodulations ont permis un changement du profil d activité de 5-HT1A vers 5-HT7. Une deuxième famille de composés à structure furo- ou pyrano[2,3-b] pyridinique constitue des analogues azotés d un des plus intéressants agonistes sélectifs 5-HT7 actuels. La synthèse de ces dérivés a été conduite via la mise en oeuvre d une étape clé de cycloaddition intramoléculaire de Diels-Alder à partir de 1,2,4-triazines judicieusement fonctionnalisées en 3 par une chaine aminoalkynol. Cette méthodologie nous a permis de faire varier les substituants alkyle de l amine, la nature et la position du motif aryle sur le noyau pyridinique, ainsi que la taille du cycle non-aromatique. La synthèse d une dernière famille de dérivés bisaryliques a enrichi les études de relation structure-activité, connues dans la littérature, associées à ce type de ligands 5-HT7. La variation du cycle aromatique central (phényle, 1,3-diazine et 1,2,4- triazine) a révélé d importantes conséquences sur l affinité des molécules.Among all the neurotransmitters identified up-to-date, serotonin (5-Hydroxytryptamine, 5-HT) is mediated by the most complex system of receptors. The 5-HT7 receptors are the latest discovered (1993) and have many implications both in the central nervous system and in peripheral tissues. The therapeutic potential of new 5- HT7 ligands, selective over the other GPCRs, motivated our research project. Our studies were focused on the design of three different classes of 5-HT7 ligands. The first class was built on a benzimidazolone scaffold. Various modulations afforded a shift of the affinity profile from the 5-HT1ARs to the 5-HT7Rs. A second class of 3-aminofuro- or pyrano[2,3-b]pyridines are in fact the heteroanalogues of one of the most interesting current 5-HT7 selective agonists: the 3-aminochromans. Their synthesis involved an intramolecular Diels-Alder cycloaddition key step starting from a 1,2,4-triazine judiciously substituted in 3 with a convenient aminoalkynol. The developed methodology afforded the variation of the substituents on the amine moiety, of the aromatic substituent and its position on the pyridinic core and of the non-aromatic ring size. A last class of bisarylic derivatives further explored the SAR tendencies of this type of 5-HT7 ligands by modulating the main aromatic scaffold in the benzene, pyrimidine and 1,2,4-triazine series.ORLEANS-SCD-Bib. electronique (452349901) / SudocSudocFranceF

OPTIMIZATION OF A HPLC ANALYSIS METHOD FOR TAURINE AND CAFFEINE IN ENERGY DRINKS

This paper presents the optimization of a rapid, inexpensive, reliable and selective isocratic high performance liquid chromatographic (HPLC) method for the simultaneous determination of caffeine and taurine in energy drinks with two common detectors in series: evaporating light scattering detector (ELSD) and an ultraviolet (UV) detector. Satisfactory analysis results were obtained on an Astec apHera NH2 column using methanol/water (30:70 v/v) as mobile phase. The optimized method was used for the analysis of commercial energy drinks containing large amounts of carbohydrates (100 g·L-1) and considerably lower amounts of taurine and caffeine (4 and 0.6 g·L-1, respectively). The advantages of this method consist of its lack of preliminary samples treatment and also the fact that basic LC instrumentation was employed

Synthèse et fonctionnalisation d'hétérocycles azotés polycycliques (application à l'obtention de composés antitumoraux)

Le cancer constitue aujourd'hui la deuxième cause de mortalité dans l'ensemble des pays développés après les maladies cardiovasculaires. De nombreuses équipes de chimistes travaillent sur la synthèse de nouvelles molécules ayant une forte probabilité d'être antitumorales. Dans cette optique, des recherches effectuées au sein de notre Laboratoire ont fait état de la synthe se arynique, de la réactivité et du potentiel caractère anticancéreux d'une nouvelle famille d'antitumoraux les dihydrodipyridopyrazines. Dans cette thèse, nous réalisons une étude approfondie de la réaction de cyclisation hétarynique et de la fonctionnalisation des dihydrodipyridopyrazines via des réactions de couplage pallado-catalysées et des séquences d'ortho-lithiation. Nous décrivons également l'accès à des dérivés pentacycliques inconnus jusqu'à ce jour qui ont révélé des propriétés chimiques intéressantes. Simultanément, des recherches pharmacologiques ont été menées.ORLEANS-BU Sciences (452342104) / SudocSudocFranceRomaniaFRR

EFFECTS OF HORMONES ADDITION FOR IN VITRO PLANT DEVELOPMENT OF CALENDULLA OFFICINALIS

The current study presented in vitro plant development of Calendula officinalis on MS (Murashige and Skoog) medium supplemented with different formula of hormones. The morphogenetic response was evaluated by recording the number of plantlets, the plant height and weight. The results showed that small amounts of hormones can improve the plantlets growth in the case of Calendula officinalis

Perspectives for Quality Evaluation of Some Mineral Waters from Slanic Moldova

In the present study, using a combination of several analytical techniques such as conductometry/total dissolved solids (TDS), pH-metry, ICP-MS and UV-Vis spectrometry, 38 parameters (Na, K, Mg, Ca, Al, Fe, B, Li, Cr, Mn, Ni, Cu, Zn, Se, Sr, Ag, Cd, Ba, Pb, Be, V, Co, Ga, As, Rb, Cs, Hg, Tl, U, F−, Cl−, SO42−, NO3−, NO2−, HCO3−, CO2, electric conductivity (EC)/TDS and pH) for seven natural mineral waters (springs 1 bis, 5, 10, 14, 15, Sonda 2 and Sfantul Spiridon) from the Slanic Moldova area (Romania) were evaluated. Our data were compared with the historical chemical analyses records and also with the limits established by international and Romanian regulations for qualitative evaluation of natural mineral waters. In the case of the Evolution of the mineralization degree over time, it was observed that, in the interval 1933–2021, for all the studied sources, there were variations of mineralization that could be attributed to climatic and geological changes, mode of exploitation, as well as to analysis techniques used. Although decreases in mineralization were observed between 1981 and 2006 for water sources 1 bis, 10, 15 and S2, with a slight recovery and stability period between 2006 and 2021, they have retained their characteristics over time. Moreover, spring 14 retains its status as the most mineralized spring of the seven, although it also recorded a decrease in the mineralization degree between 2013 and 2018. Even if the concentration of major and minor ions showed some variation, highlighting the diversity of the water intakes and its changes over time for some of the springs, it is noticeable that these springs have kept their characteristics over time. It was identified that Sodium (Na+) was present in all natural mineral waters but predominated in sodium chloride, sodium bicarbonate and sodium sulfate. The concentration of potassium ion has shown a fairly significant fluctuation, in 2006 being registered the lowest values for most sources: 1 bis (88.00 mg/L), 5 (6.00 mg/L), 10 (81.00 mg/L), 14 (115.00 mg/L), 15 (45.20 mg/L), S2 (11.00 mg/L). By means of ICP-MS, trace elements that have never before been tested or reported were identified, thus completing the chemical fingerprint of these natural mineral waters to increase their value for routine or therapeutic uses or further sustainable exploitation

Perspectives for Quality Evaluation of Some Mineral Waters from Slanic Moldova

In the present study, using a combination of several analytical techniques such as conductometry/total dissolved solids (TDS), pH-metry, ICP-MS and UV-Vis spectrometry, 38 parameters (Na, K, Mg, Ca, Al, Fe, B, Li, Cr, Mn, Ni, Cu, Zn, Se, Sr, Ag, Cd, Ba, Pb, Be, V, Co, Ga, As, Rb, Cs, Hg, Tl, U, F−, Cl−, SO42−, NO3−, NO2−, HCO3−, CO2, electric conductivity (EC)/TDS and pH) for seven natural mineral waters (springs 1 bis, 5, 10, 14, 15, Sonda 2 and Sfantul Spiridon) from the Slanic Moldova area (Romania) were evaluated. Our data were compared with the historical chemical analyses records and also with the limits established by international and Romanian regulations for qualitative evaluation of natural mineral waters. In the case of the Evolution of the mineralization degree over time, it was observed that, in the interval 1933–2021, for all the studied sources, there were variations of mineralization that could be attributed to climatic and geological changes, mode of exploitation, as well as to analysis techniques used. Although decreases in mineralization were observed between 1981 and 2006 for water sources 1 bis, 10, 15 and S2, with a slight recovery and stability period between 2006 and 2021, they have retained their characteristics over time. Moreover, spring 14 retains its status as the most mineralized spring of the seven, although it also recorded a decrease in the mineralization degree between 2013 and 2018. Even if the concentration of major and minor ions showed some variation, highlighting the diversity of the water intakes and its changes over time for some of the springs, it is noticeable that these springs have kept their characteristics over time. It was identified that Sodium (Na+) was present in all natural mineral waters but predominated in sodium chloride, sodium bicarbonate and sodium sulfate. The concentration of potassium ion has shown a fairly significant fluctuation, in 2006 being registered the lowest values for most sources: 1 bis (88.00 mg/L), 5 (6.00 mg/L), 10 (81.00 mg/L), 14 (115.00 mg/L), 15 (45.20 mg/L), S2 (11.00 mg/L). By means of ICP-MS, trace elements that have never before been tested or reported were identified, thus completing the chemical fingerprint of these natural mineral waters to increase their value for routine or therapeutic uses or further sustainable exploitation

Conception, synthèse, évaluation biologique d’agonistes du récepteur 5-HT7 pour le traitement de la douleur

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