Chemistry Weekly Seminar - Placid Orji, PhD Student
Placid Orji, PhD student in the Department of Chemistry, University of Saskatchewan, will present a seminar at 1:30 pm in Thorvaldson 159.
Title
Synthesis of fluorinated cannabinoid derivatives and the GAT compounds: Towards PET radiotracers for imaging the cannabinoid receptor
Abstract
The endocannabinoid system includes cannabinoid receptors, which are modulated by their endogenous ligands (endocannabinoids), and the enzymes that synthesize and degrade those endocannabinoids. The endocannabinoid system modulates the release of other neurotransmitters through the type 1 cannabinoid receptor (CB1). CB1 and other cannabinoid receptors may also be modulated by cannabinoids from the Cannabis sativa plant and synthetic derivatives of those cannabinoids. Defects in CB1 expression or endocannabinoid transmission have been associated with several neuropsychiatric disorders, and consequently, CB1 is considered a therapeutic target. However, identifying the most promising cannabinoid-based therapeutics with suitable drug-like properties has been challenging due to their high lipophilicity and complex pharmacology. Therefore, employing functional imaging techniques such as positron emission tomography (PET), would be useful to quantify the expression and activity of CB1 in disease as well as help guide the development of novel ligands as potential therapeutic compounds that can activate or inhibit the endocannabinoid system.
In this project, we prepared various fluorinated derivatives of tetrahydrocannabinol-type, cannabidiol-type, cannabicyclol-type, and cannabichromene-type plant cannabinoids from Cannabis sativa (Figure below) and synthetic cannabinoids as PET tracer candidates. Once prepared, the PET tracer candidates were tested for binding affinity and agonistic activity towards CB1 in assays using CHO-K1 cells that stably express CB1. Next, we identified the fluorinated candidates with brain uptake using assays that identify which compounds evoke tetrad-like responses, characteristic of CB1 binding in vivo, using C57BL/6 mice. Four derivatives that had biological activity in vivo were labeled with 18F followed by biodistribution, and microPET imaging studies in mice.
Date: Friday, January 12
Time: 1:30 pm
Place: Thorvaldson 159