"Photo-Rimonabant": Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar "Cis-On" CB₁R Antagonist.

ABSTRACT: Human cannabinoid receptor type 1 (hCB₁R) plays important roles in the regulation of appetite and development of addictive behaviors. Herein, we describe the design, synthesis, photocharacterization, molecular docking, and in vitro characterization of "photo-rimonabant", i.e., azo-derivatives of the selective hCB₁R antagonist SR1411716A (rimonabant). By applying azo-extension strategies, we yielded compound 16a, which shows marked affinity for CB₁R (K_{i (cis form)} = 29 nM), whose potency increases by illumination with ultraviolet light (CB₁R K_itrans/cis ratio = 15.3). Through radioligand binding, calcium mobilization, and cell luminescence assays, we established that

SUBMITTER: Rodriguez-Soacha DA 

PROVIDER: S-EPMC9016771 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature