title: Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.
abstract: Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ-, δ- and μ-opioid receptors. Most of the analogues show high affinity to the κ-opioid receptor. Methyl malonyl derivative 4 shows the highest binding affinity (Ki=2nM), analogues 5, 7, and 14 exhibit significant affinity for the κ-receptor (Ki=21, 36 and 39nM).
authors.affiliation: Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA.
authors.forename: Prabhakar R
authors.initials: PR
authors.lastname: Polepally
authors.forename: Kate
authors.initials: K
authors.lastname: White
authors.forename: Eyal
authors.initials: E
authors.lastname: Vardy
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Roth
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Zjawiony
mesh_terms: D001892:Camphanes; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008968:Molecular Conformation; D053723:Panax notoginseng; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D027544:Salvia / Q000737:chemistry; D027561:Salvia miltiorrhiza; D013329:Structure-Activity Relationship
chemical_list: D001892:Camphanes; D045785:Diterpenes, Clerodane; D004365:Drugs, Chinese Herbal; D017473:Receptors, Opioid, kappa; C000604051:danshen dripping pill; C090499:salvinorin A