TY - JOUR
T1 - Novel acylethanolamide derivatives that modulate body weight through enhancement of hypothalamic pro-opiomelanocortin (POMC) and/or decreased neuropeptide y (NPY)
AU - Avraham, Yosefa
AU - Katzhendler, Jehoshua
AU - Vorobeiv, Lia
AU - Merchavia, Shira
AU - Listman, Chana
AU - Kunkes, Eithan
AU - Harfoush, Fida'
AU - Salameh, Sawsan
AU - Ezra, Aviva F.
AU - Grigoriadis, Nikolaos C.
AU - Berry, Elliot M.
AU - Najajreh, Yousef
PY - 2013/3/14
Y1 - 2013/3/14
N2 - Newly synthesized acylethanolamide derivatives oleoyl-l-valinolamide (1), oleoyl-d-valinolamide (2), elaidoyl-l-valinolamide (3), elaidoyl-d-valinolamide (4) stearoyl-l-valinolamide (5), and palmitoyl-l-valinolamide (6) were investigated in mice as antiobesity compounds. Compounds 1, 2, 5, 6 significantly decreased body weight by 6.57% following eight injections of 1 mg/kg ip during 39 days, while 3 and 4 showed no such activity. Receptor binding indicated that no compound activated CB1, CB2, PPARα, or TRPV1 receptors. Hypothalamic RT-PCR showed that mRNA expression of the anorexigenic genes POMC and CART was up-regulated by 1, 2, 5 and 1, 2, respectively, while that of the orexigenic genes NPY and CaMKK2 was down-regulated by the respective compounds 1, 5, 6 and 1, 2, 5. Oleoyl-l-valinolamide enhances anorectic pathways and lead to decreased glucose levels, enhanced locomotor activity, and improved cognition. Effects of oleoyl-l-valinolamide on weight were dose-dependent, and it could be given orally. 1, 2, 4, 5 down-regulated FAAH mRNA expression.
AB - Newly synthesized acylethanolamide derivatives oleoyl-l-valinolamide (1), oleoyl-d-valinolamide (2), elaidoyl-l-valinolamide (3), elaidoyl-d-valinolamide (4) stearoyl-l-valinolamide (5), and palmitoyl-l-valinolamide (6) were investigated in mice as antiobesity compounds. Compounds 1, 2, 5, 6 significantly decreased body weight by 6.57% following eight injections of 1 mg/kg ip during 39 days, while 3 and 4 showed no such activity. Receptor binding indicated that no compound activated CB1, CB2, PPARα, or TRPV1 receptors. Hypothalamic RT-PCR showed that mRNA expression of the anorexigenic genes POMC and CART was up-regulated by 1, 2, 5 and 1, 2, respectively, while that of the orexigenic genes NPY and CaMKK2 was down-regulated by the respective compounds 1, 5, 6 and 1, 2, 5. Oleoyl-l-valinolamide enhances anorectic pathways and lead to decreased glucose levels, enhanced locomotor activity, and improved cognition. Effects of oleoyl-l-valinolamide on weight were dose-dependent, and it could be given orally. 1, 2, 4, 5 down-regulated FAAH mRNA expression.
UR - http://www.scopus.com/inward/record.url?scp=84875199116&partnerID=8YFLogxK
U2 - 10.1021/jm300484d
DO - 10.1021/jm300484d
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C2 - 23384387
AN - SCOPUS:84875199116
SN - 0022-2623
VL - 56
SP - 1811
EP - 1829
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 5
ER -