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Synthesis, in vitro and in vivo evaluation, and radiolabeling of aryl anandamide analogues as candidate radioligands for in vivo imaging of fatty acid amide hydrolase in the brain

Leonie wyffels UGent, Giulio G Muccioli, SYLVIE DE BRUYNE UGent, LIESELOTTE MOERMAN UGent, JOHAN SAMBRE UGent, Didier M Lambert and Filip De Vos UGent (2009) JOURNAL OF MEDICINAL CHEMISTRY. 52(15). p.4613-4622
abstract
Fatty acid amide hydrolyase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids in the brain. Imaging FAAH in vivo using PET or SPECT is important to deeper understanding of its role in neuropsychiatric disorders. However, at present, no radioligand is available for mapping the enzyme in vivo. Here, we synthesized 18 aryl analogues of anandamide, FAAH's endogenous substrate, and in vitro evaluated their potential as metabolic trapping tracers. Interaction studies with recombinant FAAH revealed good to very good interaction of the methoxy substituted aryl anandamide analogues 17, 18, 19, and 20 with FAAH and they were identified as competing substrates, Compounds 17 and 18 did not display significant binding to CB1 and CB2 cannabinoid receptors and stand out as potential candidate metabolic trapping tracers. They were successfully labeled with C-11 in good yields and high radiochemical purity and displayed brain uptake in C57BL/6J mice. Radioligands [C-11]-17 and [C-11]-18 merit further investigation in vivo.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
SUBSTRATE-SPECIFICITY, MULTIPLE-SCLEROSIS, CANNABINOID RECEPTORS, PROBLEM DRUG-USE, ANXIETY-LIKE BEHAVIOR, POSITRON-EMISSION-TOMOGRAPHY, ANTIDEPRESSANT-LIKE ACTIVITY, RAT MODEL, AMIDOHYDROLASE, FAAH
journal title
JOURNAL OF MEDICINAL CHEMISTRY
J. Med. Chem.
volume
52
issue
15
pages
4613 - 4622
Web of Science type
Article
Web of Science id
000268661600008
JCR category
CHEMISTRY, MEDICINAL
JCR impact factor
4.802 (2009)
JCR rank
3/46 (2009)
JCR quartile
1 (2009)
ISSN
0022-2623
DOI
10.1021/jm900324e
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1234131
handle
http://hdl.handle.net/1854/LU-1234131
date created
2011-05-24 15:06:25
date last changed
2011-05-25 11:21:39
@article{1234131,
  abstract     = {Fatty acid amide hydrolyase (FAAH) is one of the main enzymes responsible for terminating the signaling of endocannabinoids in the brain. Imaging FAAH in vivo using PET or SPECT is important to deeper understanding of its role in neuropsychiatric disorders. However, at present, no radioligand is available for mapping the enzyme in vivo. Here, we synthesized 18 aryl analogues of anandamide, FAAH's endogenous substrate, and in vitro evaluated their potential as metabolic trapping tracers. Interaction studies with recombinant FAAH revealed good to very good interaction of the methoxy substituted aryl anandamide analogues 17, 18, 19, and 20 with FAAH and they were identified as competing substrates, Compounds 17 and 18 did not display significant binding to CB1 and CB2 cannabinoid receptors and stand out as potential candidate metabolic trapping tracers. They were successfully labeled with C-11 in good yields and high radiochemical purity and displayed brain uptake in C57BL/6J mice. Radioligands [C-11]-17 and [C-11]-18 merit further investigation in vivo.},
  author       = {wyffels, Leonie and Muccioli, Giulio G and DE BRUYNE, SYLVIE and MOERMAN, LIESELOTTE and SAMBRE, JOHAN and Lambert, Didier M and De Vos, Filip},
  issn         = {0022-2623},
  journal      = {JOURNAL OF MEDICINAL CHEMISTRY},
  keyword      = {SUBSTRATE-SPECIFICITY,MULTIPLE-SCLEROSIS,CANNABINOID RECEPTORS,PROBLEM DRUG-USE,ANXIETY-LIKE BEHAVIOR,POSITRON-EMISSION-TOMOGRAPHY,ANTIDEPRESSANT-LIKE ACTIVITY,RAT MODEL,AMIDOHYDROLASE,FAAH},
  language     = {eng},
  number       = {15},
  pages        = {4613--4622},
  title        = {Synthesis, in vitro and in vivo evaluation, and radiolabeling of aryl anandamide analogues as candidate radioligands for in vivo imaging of fatty acid amide hydrolase in the brain},
  url          = {http://dx.doi.org/10.1021/jm900324e},
  volume       = {52},
  year         = {2009},
}

Chicago
wyffels, Leonie, Giulio G Muccioli, SYLVIE DE BRUYNE, LIESELOTTE MOERMAN, JOHAN SAMBRE, Didier M Lambert, and Filip De Vos. 2009. “Synthesis, in Vitro and in Vivo Evaluation, and Radiolabeling of Aryl Anandamide Analogues as Candidate Radioligands for in Vivo Imaging of Fatty Acid Amide Hydrolase in the Brain.” Journal of Medicinal Chemistry 52 (15): 4613–4622.
APA
wyffels, L., Muccioli, G. G., DE BRUYNE, S., MOERMAN, L., SAMBRE, J., Lambert, D. M., & De Vos, F. (2009). Synthesis, in vitro and in vivo evaluation, and radiolabeling of aryl anandamide analogues as candidate radioligands for in vivo imaging of fatty acid amide hydrolase in the brain. JOURNAL OF MEDICINAL CHEMISTRY, 52(15), 4613–4622.
Vancouver
1.
wyffels L, Muccioli GG, DE BRUYNE S, MOERMAN L, SAMBRE J, Lambert DM, et al. Synthesis, in vitro and in vivo evaluation, and radiolabeling of aryl anandamide analogues as candidate radioligands for in vivo imaging of fatty acid amide hydrolase in the brain. JOURNAL OF MEDICINAL CHEMISTRY. 2009;52(15):4613–22.
MLA
wyffels, Leonie, Giulio G Muccioli, SYLVIE DE BRUYNE, et al. “Synthesis, in Vitro and in Vivo Evaluation, and Radiolabeling of Aryl Anandamide Analogues as Candidate Radioligands for in Vivo Imaging of Fatty Acid Amide Hydrolase in the Brain.” JOURNAL OF MEDICINAL CHEMISTRY 52.15 (2009): 4613–4622. Print.