Planta Med 2013; 79 - P42
DOI: 10.1055/s-0033-1336484

Synthesis and In Vitro Biological Evaluation of New Dicarboxylic Ester-type Salvinorin A Analogs

PR Polepally 1, BL Roth 2, K White 2, D Ferreira 1, 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, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen [1]. It is a highly selective kappa-opioid receptor (KOR) agonist [2]. To better understand the ligand-receptor interactions, a new 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 analogs have shown high affinity to κ-opioid receptor. Methyl malonyl derivative has shown higher binding affinity than parent compound salvinorin A at KOR. The ethyl malonyl ligand, methyl succinyl analog and methyl fumaryl derivative have also shown significant affinity for κ-receptor.

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] Valdes LJ, et al. (1983)J Ethnopharmacol, 7: 287 – 312. [2] Roth BL, et al. (2002) Proceedings of the National Academy of Sciences, 99: 11934 – 11939.