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conferenceseries.com
Volume 8 Medicinal Chemistry
ISSN: 2161-0444 Medicinal Chemistry 2018
June 14-15, 2018
June 14-15, 2018 | Barcelona, Spain
10th World Congress on
Medicinal Chemistry and Drug Design
Discovery and structure - activity relation study of small-molecule as CB2 selective ligand
Amer Tarawneh1, 2, Lo’ay Al-Momani1, Francisco León2, Janet Lambert2, Anastassiya V Gadetskaya3 and Stephen J Cutler2
1Tafila Technical University, Jordan
2The University of Mississippi, USA
3Al-Farabi Kazakh National University, Kazakhstan
The CB1 receptor was originally called the cannabinoid receptor before the CB2 receptor was discovered, but CB1 did
not explain the immunomodulatory effects of cannabis, which were already well-documented at this time. In 1993, this
effect was accounted by the finding of the CB2 receptor in a human promyelocytic leukemia cell line. Both CB1 and CB2 are
G-protein coupled receptors, which share a 48% sequence identity. There have been numerous studies on the pharmacology
of CB2, giving it the name receptor with an identity crisis. Because CB2 (unlike CB1) is largely not expressed in the central
nervous system, but rather in the spleen and immune cells, it is known as the peripheral cannabinoid receptor soon after
its discovery. When CB2 expression was found in the neurons and in the microglial cells of the brain, this terminology
was determined to be inaccurate, and CB2 expression has since been shown to be correlated with neuroinflammation. A
2005 study showed a 200-fold up regulation of the CB2 receptors in the microglial cells in an in vitro model of autoimmune
encephalomyelitis many of these studies are now considered questionable because further research has shown that the anti-
CB2 antibodies used in these Immunohistochemical methods have non-specific binding with other proteins. However, the
immunomodulatory effects of CB2 remain unchallenged. In addition, CB2 expression has more recently been associated with
neurodegenerative diseases such as Huntington and Alzheimer. CB2-selective Positron Emission Tomography (PET) tracers
in Alzheimer’s mice have demonstrated increased expression of CB2, concomitant with the formation of amyloid-beta plaques.
This suggests that CB2 PET tracers may have potential as a diagnostic tool for neuro-inflammation. In order to counteract
these effects, studies are underway to develop selective CB2 ligand. This research began with testing of a series of isoxazole and
triazole derivatives, which lead to discovery of a novel ligand highly selective for cannabinoid receptor 2. Compound ATJ-31
produced a concentration-dependent inhibition of specific [3H] - CP55, 940 (CB2) binding with a Ki value of 105 nM, while
no binding affinity toward CB1 receptor was observed. The current study aims to design, synthesize and biologically evaluate
potential CB2 receptor ligand.
Recent Publications
1. Savonenko A V, Melnikova T, Wang Y, Ravert H, Gao Y, Koppel J, Lee D, Pletnikova O, Cho E, Sayyida N, Hiatt A,
Troncoso J, Davies P, Dannals R F, Pomper M G and Horti A G.(2015) Cannabinoid CB2 Receptors in a Mouse Model
of Aβ Amyloidosis: Immunohistochemical Analysis and Suitability as a PET Biomarker of Neuroinflammation. PLoS
ONE 10(6):e0129618.
2. Baek J H, Darlington C L, Smith P F and Ashton J C. (2013) Antibody testing for brain immunohistochemistry: Brain
immunolabeling for the cannabinoid CB2 receptor. Journal of Neuroscience Methods 216(2):p. 87.
3. Marchalant Y, Brownjohn P W, Bonnet A, Kleffmann T and Ashton J C (2014) Validating Antibodies to the
Cannabinoid CB2 Receptor: Antibody Sensitivity Is Not Evidence of Antibody Specificity. Journal of Histochemistry
& Cytochemistry. 62(6): p. 395.
4. Di Marzo V, Stella N and Zimmer A (2015) Endocannabinoid signalling and the deteriorating brain. Nat Rev Neurosci.
16(1): p. 30.
5. Savonenko A V, Melnikova T, Wang Y, Ravert H, Gao Y, Koppel J, Lee D, Pletnikova O, Cho E, Sayyida N, Hiatt A,
Troncoso J, Davies P, Dannals R F, Pomper M G and Horti A G (2015) Cannabinoid CB2 Receptors in a Mouse Model
of Aβ Amyloidosis: Immunohistochemical Analysis and Suitability as a PET Biomarker of Neuroinflammation. PLoS
ONE. 10(6): p. e0129618.
Amer Tarawneh et al., Med chem (Los Angeles) 2018, Volume 8
DOI: 10.4172/2161-0444-C1-039