Synthesis and biological evaluation of C-12 triazole and oxadiazole analogs of salvinorin A.
Lu Yang, Wei Xu, Feng Chen, Lee-Yuan Liu-Chen, Zhongze Ma, David Y W Lee
Bioorganic & Medicinal Chemistry Letters March 1, 2009 DOI: 10.1016/j.bmcl.2009.01.078 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Salvia divinorum |
| Key findings | C-12 triazole analogs of salvinorin A show negligible binding affinity at opioid receptors, and the oxadiazole analog exhibits very low affinities and no antagonism, indicating that electronic and hydrophobic factors at C-12 are critical for kappa-opioid receptor affinity. |
Abstract
Salvinorin A (1), the main active ingredient of Salvia divinorum, is a potent and selective kappa-opioid receptor (KOPR) agonist. A series of C-12 triazole analogs and the oxadiazole (4) analog of 1 are synthesized and screened for binding affinity at kappa, mu (MOPR), or delta (DOPR). Surprisingly, all triazole analogs have shown negligible binding affinity at opioid receptors and the oxadiazole 4, a reported MOPR and KOPR antagonist, exhibits very low affinities to opioid receptors and no antagonism in our binding assays. These results suggest that electronic factors that may affect either the electron density of hydrogen bond acceptor at C-12 or hydrophobic interactions between C-12 moiety and KOPR are critical to C-12 analog's affinity for KOPR.
Comparable studies
Other experimental studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. | 2002 | Experimental study | |
| Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Cloned human kappa-opioid receptors expressed in human embryonic kidney-293 cells and... | 2004 | Experimental study | |
| Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. Animal model | 2014 | Experimental study | |
| Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors. | 2005 | Experimental study | |
| Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Rat brain striatum homogenates | 2009 | Laboratory experiment |
Citations in the library
Cited by 5
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Synthesis of neoclerodane diterpenes and their pharmacological effects. Topics in current chemistry 2011
- A Review of Salvinorin Analogs and their Kappa-Opioid Receptor Activity Bioorganic & Medicinal Chemistry Letters March 12, 2018
- Semisynthesis and Kappa-Opioid Receptor Activity of Derivatives of Columbin, a Furanolactone Diterpene. Journal of Natural Products July 28, 2017
- Enantioselective Access to Key Intermediates for Salvinorin A and Analogues European journal of organic chemistry May 1, 2011
Cites 9
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors. Biochemistry June 21, 2005
- Synthetic studies of neoclerodane diterpenes from Salvia divinorum: semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A. Journal of Natural Products 2006
- 2-Methoxymethyl-salvinorin B is a potent kappa opioid receptor agonist with longer lasting action in vivo than salvinorin A. Journal of Pharmacology and Experimental Therapeutics March 2008
- Synthetic studies of neoclerodane diterpenes from Salvia divinorum: preparation and opioid receptor activity of salvinicin analogues. Journal of Medicinal Chemistry July 26, 2007
and 4 more in the library