Design and synthesis of natural product-based ligands with high affinity to the kappa-opioid receptor
JK Zjawiony, PR Polepally, B.l. Roth, Vincent Setola, Eyal Vardy
Planta Medica August 1, 2011 DOI: 10.1055/s-0031-1282127 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Citations | 10 |
| Key points | The authors propose that new salvinorin A derivatives with Michael acceptor-type functional groups were synthesized and evaluated in vitro, aiming to produce high-affinity KOR ligands. However, no specific results are reported in the abstract. |
Abstract
Psychoactive natural products play an important role in the discovery and development of new drugs for the treatment of central nervous system (CNS) disorders. Our studies are focusing on identification of plant metabolites responsible for CNS activity and designing new ligands with high affinity to CNS receptors. Salvinorin A, the most potent naturally occurring hallucinogen isolated from the plant Salvia divinorum Epling & Játiva (Lamiaceae), has received great attention since the kappa-opioid receptor (KOR) was identified as its principal molecular target. Previously, extensive efforts were made to understand how salvinorin A binds to and activates KOR [1–4]. Our goal was to design a series of ligands with high affinity to KOR to further explore the ligand-receptor interactions at the molecular level. Following the synthesis of 22-thiocyanatosalvinorin A [5], the first irreversible KOR ligand, we now report the synthesis and biological evaluation in vitro of new salvinorin A derivatives with Michael acceptor-type functional groups. Figure 1: Synthesis of salvinorin A derivatives with Michael acceptor-type functional groups