Inspired by the biological activity of gliotoxin (fungal metabolite) as histamine receptor 1 ligand, we have designed and synthesized a set of monocyclic, bicyclic, and tricyclic diketopiperazine-based ligands. Out of tested analogs, the binding assay identified compounds with varying selectivity degrees towards different subtypes of opioid receptors. The selected KOR ligand with the optimal pharmacokinetic profile was tested <i>in vivo</i> using the spinal nerve ligation (SNL) neuropathic pain model in rats. Our results demonstrate the tested compound's ability to modulate the sensory and emotional pain-related behaviors in rats following 3 mg/kg intraperitoneal administration. These findings are supported by the existing data on the role of KOR-mediated signaling in establishing symptoms associated with chronic pain. Our compounds' chemical novelty and the observed in-vivo efficacy provide a path for further development of these chemical agents as potential candidates for pain therapy.

Design, synthesis, and <i>in-vivo</i> evaluation of selective KOR ligands

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Design, synthesis, and in-vivo evaluation of selective KOR ligands