TY - JOUR
T1 - Development of the first potential covalent inhibitors of anandamide cellular uptake
AU - Moriello, Aniello Schiano
AU - Balas, Laurence
AU - Ligresti, Alessia
AU - Cascio, Maria Grazia
AU - Durand, Thierry
AU - Morera, Enrico
AU - Ortar, Giorgio
AU - Di Marzo, Vincenzo
PY - 2006/4/1
Y1 - 2006/4/1
N2 - On the basis of the chemical structures of two previously developed metabolically stable and relatively potent inhibitors of anandamide uptake, OMDM-1,2, two series of potential covalent inhibitors of anandamide cellular reuptake, which might be used for the molecular characterization of the protein(s) involved in the membrane transport of endocannabinoids, have been designed and synthesized. Most of the compounds inhibited uptake to a varied extent and in a generally enantio-sensitive manner when co-incubated with [ 14C]anandamide, but only three of them, the photoactivatable 1a (OMDM-37), 1b (OMDM-39), and 8 (Lo395), also produced a significant inhibition of uptake following the preincubation only of the cells, and this effect was significantly enhanced following UV exposure only in the case of 8. None of the new compounds inhibited [14C]anandamide hydrolysis with IC 50 < 50 μM, except for 1b.
AB - On the basis of the chemical structures of two previously developed metabolically stable and relatively potent inhibitors of anandamide uptake, OMDM-1,2, two series of potential covalent inhibitors of anandamide cellular reuptake, which might be used for the molecular characterization of the protein(s) involved in the membrane transport of endocannabinoids, have been designed and synthesized. Most of the compounds inhibited uptake to a varied extent and in a generally enantio-sensitive manner when co-incubated with [ 14C]anandamide, but only three of them, the photoactivatable 1a (OMDM-37), 1b (OMDM-39), and 8 (Lo395), also produced a significant inhibition of uptake following the preincubation only of the cells, and this effect was significantly enhanced following UV exposure only in the case of 8. None of the new compounds inhibited [14C]anandamide hydrolysis with IC 50 < 50 μM, except for 1b.
UR - http://www.scopus.com/inward/record.url?scp=33645688894&partnerID=8YFLogxK
U2 - 10.1021/jm051226l
DO - 10.1021/jm051226l
M3 - Article
C2 - 16570928
AN - SCOPUS:33645688894
SN - 0022-2623
VL - 49
SP - 2320
EP - 2332
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 7
ER -