Docking study, synthesis, and in vitro evaluation of fluoro-MADAM derivatives as SERT ligands for PET imaging.
In order to predict affinity of new diphenylsulfides for the serotonin transporter (SERT), a molecular modeling model was used to compare potential binding affinity of new compounds with known potent ligands. The aim of this study is to identify a suitable PET radioligand for imaging the SERT, new derivatives, and their precursors for a C-11 or F-18 radiolabeling, were synthesized. Two fluorinated derivatives displayed good in vitro affinity for the SERT (K(i)=14.3+/-1 and 10.1+/-2.7 nM) and good selectivity toward the other monoamine transporters as predicted by the docking study.
Mavel
Sylvie
S
INSERM U930, 37000 TOURS, France; Université François-Rabelais de Tours, 37000 TOURS, France. sylvie.mavel@univ-tours.fr
Vercouillie
Johnny
J
Garreau
Lucette
L
Raguza
Tiziana
T
Ravna
Aina Westrheim
AW
Chalon
Sylvie
S
Guilloteau
Denis
D
Emond
Patrick
P
D000465:Algorithms; D001596:Benzylamines / Q000138:chemical synthesis; D002250:Carbon Radioisotopes / Q000737:chemistry; D002460:Cell Line; D003952:Diagnostic Imaging / Q000379:methods*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000473:pathology; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins / Q000737:chemistry / Q000378:metabolism*
D001596:Benzylamines; D002250:Carbon Radioisotopes; D005462:Fluorine Radioisotopes; D008024:Ligands; D026901:Membrane Transport Proteins; C470437:N,N-dimethyl-2-(2-amino-4-methylphenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins