Planta Med 2013; 79 - P44
DOI: 10.1055/s-0033-1336486

Synthesis and Biological Evaluation of New Salvinorin B-Sulfonate Ester Ligands to Opioid Receptors

PR Polepally 1, BL Roth 2, K White 2, E Vardy 2, JK Zjawiony 1
  • 1Department of Pharmacognosy, and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677 – 1848, USA
  • 2Department of Pharmacology, School of Medicine and Division of Medicinal Chemistry and Natural Products, School of Pharmacy, NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, NC 27599, USA

Salvinorin A, a major metabolite isolated from the leaves of Salvia divinorum, is a neoclerodane diterpenoid with a strong hallucinogenic activity. It has been shown to have high affinity and selectivity for kappa opioid receptor (KOR) [1]. Salvinorin A represents an attractive lead compound for drug development due to its strong effects on human mood and low toxicity. Over the past decade numerous derivatives and analogues of salvinorin A were synthesized showing a broad range of KOR affinities [2]. To better understand the ligand-KOR interactions, we synthesized a series of new salvinorin B-sulfonate ester ligands and evaluated them for binding affinity to k, µ and δ-opioid receptors.

Acknowledgements: This work was supported by the NIH Grant R01 DA017204 and the NIMH Psychoactive Drug Screening Program (PDSP), University of North Carolina at Chapel Hill, NC 27599. References: [1] Roth BL, et al. (2002) Proceedings of the National Academy of Sciences, 99: 11934 – 11939. [2] Cunningham CW, et al. (2011) Pharmacol Rev, 63: 316 – 347.