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DOI: 10.1055/s-0032-1320925
New salvinorin A – Derived ligands to opioid receptors
The neoclerodane diterpenoid salvinorin A is a major metabolite isolated from the leaves of psychoactive plant Salvia divinorum. It is a highly selective κ-opioid receptor (KOR) agonist and is the most potent naturally occurring hallucinogen. It gained significant scientific interest, being the only non-nitrogenous KOR agonist with no apparent structural similarity to other ligands. Previously, extensive efforts were made to understand how salvinorin A binds and activates the receptor. Our goal is to design a series of salvinorin A-ligands with high affinity to KOR in order to further explore the ligand-receptor interactions at the molecular level. In continuation of our research towards irreversible ligands, we synthesized a series of new C-2 modified salvinorin A derivatives and evaluated them for binding affinity to opioid receptors. A majority of the analogs have shown high affinity to KOR, and some of them have exhibited dual affinity to κ- and µ-opioid receptors.