, Tournier 2 , Thomas Cailly 1 , Cédric Lecoutey 1, *, Sophie Corvaisier 1 , Audrey Davis 1 , Céline Ballandonne 1 , Philippe Millet 2 , Frédéric Fabis 1 , Patrick Dallemagne 1 and Christophe Rochais 1
, CH-1225 Genève, Switzerland * Correspondence: cedric.lecoutey@unicaen.fr One of the greatest challenges facing medicinal chemists in the 21st century is the discovery and development of diagnostic markers of Alzheimer's disease (AD). The diagnosis of Alzheimer's patients is usually made very late, using mainly tests like the Mini-Mental State Examination or Rey-Osterrieth's figure. The establishment of an early diagnosis would allow an advanced support for a patient, potentially delaying the progression of symptoms. Serotonin 5-HT4 receptors (5-HT4R) control brain physiological functions such as learning and memory, feeding, and mood behavior as well as gastro-intestinal transit. Several major devastating illnesses could benefit from 5-HT4 receptors-directed therapy such as AD, Curr. Opin. Pharmacol, vol.2, pp.87-93, 2011.
, Several 5-HT4 ligands synthesized in the laboratory were investigated as potential ligands for MTDL Alzheimer's therapy, pp.3825-3830, 2014.
,
, using single-photon emission computed tomography (SPECT), and appear to be promising for medical applications. The 5-HT4R radiotracers must allow a quantification and a specific labeling of 5-HT4R rich regions as a reduction of 5-HT4 receptor density has been demonstrated in the brains of Alzheimer's patients, ) and for the brain imaging of 5-HT4R, vol.3, p.993, 1995.
, Tournier 2 , Thomas Cailly 1 , Cédric Lecoutey 1, *, Sophie Corvaisier 1 , Audrey Davis 1 , Céline Ballandonne 1 , Philippe Millet 2 , Frédéric Fabis 1 , Patrick Dallemagne 1 and Christophe Rochais 1
, The diagnosis of Alzheimer's patients is usually made very late, using mainly tests like the Mini-Mental State Examination or Rey-Osterrieth's figure. The establishment of an early diagnosis would allow an advanced support for a patient, potentially delaying the progression of symptoms. Serotonin 5-HT 4 receptors (5-HT 4 R) control brain physiological functions such as learning and memory, feeding, and mood behavior as well as gastro-intestinal transit. Several major devastating illnesses could benefit from 5-HT4 receptors-directed therapy such as AD, Curr. Opin. Pharmacol, vol.2, pp.87-93, 2011.
, Several 5-HT 4 ligands synthesized in the laboratory were investigated as potential ligands for MTDL Alzheimer's therapy, pp.3825-3830, 2014.
,
, using single-photon emission computed tomography (SPECT), and appear to be promising for medical applications. The 5-HT 4 R radiotracers must allow a quantification and a specific labeling of 5-HT 4 R rich regions as a reduction of 5-HT 4 receptor density has been demonstrated in the brains of Alzheimer's patients, the present project, we have chosen to present novel analogues of donecopride, a multi-target directed ligand based on the pharmacomodulation of a 5-HT 4 R partial agonist, as new potential radiotracers for SPECT imaging, vol.3, pp.3825-3830, 1995.
, Compounds were radiolabeled with 125-Iodine by the neuroimaging unit of Geneva University Hospitals (HUG), and administered by intravenous injection to rats to obtain brain autoradiograms in vitro, Br. J. Pharmacol, vol.115, pp.1387-1392, 1995.
, Université d'Angers, 42 Rue Georges Morel, 49070 Beaucouzé, France * Correspondence: alexia.ville@univ-angers.fr This inhibitor will be first tested on CatC, Garcinoic Acid, a Convenient Natural Precursor to the Attractive ?-Tocotrienol Alexia Ville *, vol.4207
, Garcinoic Acid, a Convenient Natural Precursor to the Attractive ?-Tocotrienol Alexia Ville *, Guillaume Viault, Jean-Jacques Hélesbeux and Denis Séraphin SONAS EA921, SFR QUASAV 4207
, They mainly differ by the number and the position of aromatic methyl groups and by the nature of the side chain, phytyl for T and farnesyl for T3, Vitamin E includes eight chemically distinct chromanols named ?, ?, ?, ?-tocopherols (T) and tocotrienols (T3), vol.11, p.25, 2014.
, For a long time, ?-T was considered to be the most active form of vitamin E. However, recent researches suggested T3 to be better antioxidant agents, vol.32, pp.52-73, 1999.
, Compared with T, T3 have been less studied. ?-T3 was found in several plants such as Mammea neurophylla, Hevea brasiliensi,s and Bixa orellana. Nevertheless, either its purification from easily available plant materials is tedious because of the presence of all the vitamin E isoforms (Bixa orellana, Hevea brasiliensis) or the plant materials with a high ?-T3 content are difficult to obtain, Biochem, vol.32, pp.1559-1566, 1997.
, Therefore, we thought that the semisynthesis of ?-tocotrienol from garcinoic acid could be an attractive alternative pathway, vol.10, p.25, 2017.
, For a long time, ?-T was considered to be the most active form of vitamin E. However, recent researches suggested T3 to be better antioxidant agents, Vitamin E includes eight chemically distinct chromanols named ?, ?, ?, ?-tocopherols (T) and tocotrienols (T3), vol.11, pp.52-73, 1999.
, Compared with T, T3 have been less studied. ?-T3 was found in several plants such as Mammea neurophylla, Hevea brasiliensi,s and Bixa orellana. Nevertheless, either its purification from easily available plant materials is tedious because of the presence of all the vitamin E isoforms (Bixa orellana, Hevea brasiliensis) or the plant materials with a high ?-T3 content are difficult to obtain, Biochem, vol.32, pp.65-75, 1999.
, On the other hand, large amounts of garcinoic acid (1%), a T3 derivative, from the seeds of Garcinia kola, are isolated, Heterocycles, vol.45, pp.1559-1566, 1997.
, Therefore, we thought that the semisynthesis of ?-tocotrienol from garcinoic acid could be an attractive alternative pathway