Abstract
Two 3D quantitative structure–activity relationships (3D-QSAR) models for predicting Cannabinoid receptor 1 and 2 (CB1 and CB2) ligands have been produced by way of creating a practical tool for the drug-design and optimization of CB1 and CB2 ligands. A set of 312 molecules have been used to build the model for the CB1 receptor, and a set of 187 molecules for the CB2 receptor. All of the molecules were recovered from the literature among those possessing measured Ki values, and Forge was used as software. The present model shows high and robust predictive potential, confirmed by the quality of the statistical analysis, and an adequate descriptive capability. A visual understanding of the hydrophobic, electrostatic, and shaping features highlighting the principal interactions for the CB1 and CB2 ligands was achieved with the construction of 3D maps. The predictive capabilities of the model were then used for a scaffold-hopping study of two selected compounds, with the generation of a library of new compounds with high affinity for the two receptors. Herein, we report two new 3D-QSAR models that comprehend a large number of chemically different CB1 and CB2 ligands and well account for the individual ligand affinities. These features will facilitate the recognition of new potent and selective molecules for CB1 and CB2 receptors.
Highlights
The receptors of the endocannabinoid system are the cannabinoid receptors
To facilitate the research and investigation among chemical datasets for CB1 and CB2 ligands capabilities, selectivity, and potency, we report the development of two different 3D quantitative structure–activity relationships (3D-QSAR) models
Two 3D-QSAR models for CB1 and CB2 binders were developed in this study
Summary
The receptors of the endocannabinoid system are the cannabinoid receptors. In the human body, this system is involved in different physiological processes, including memory, mood, pain-sensation, and appetite [1]. The exact physiology of CB2 receptors is still not completely understood but a number of preclinical studies support the advantage of using CB2 ligands for the treatment of different pathophysiological disorders, such as chronic pain, maintenance of bone density, reducing the progression of atherosclerotic lesions, asthma, autoimmune and inflammatory diseases, and multiple sclerosis [14,15]. The natural derived ∆9 -THC; AM11542, which is the unique tetrahydrocannabinol derivative co-crystallized with the CB1 receptor; the two most potent CB1 and CB2 agonists (MDMB-CHMINACA and MDMB-FUBINACA), and the two most selective compounds for the CB1 and CB2 receptor (AM-1220 and XLR-12).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
