Prabhakar R Polepally

Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA.

2 papers in the library · 52 citations · publishing 2013-2014

Papers

Michael acceptor approach to the design of new salvinorin A-based high affinity ligands for the kappa-opioid receptor.

European journal of medicinal chemistry October 6, 2014 Prabhakar R Polepally, Krzysztof Huben, Eyal Vardy et al. 28 citations

Salvinorin A, a compound from the plant Salvia divinorum, binds strongly and selectively to the κ-opioid receptor (KOR). A new series of salvinorin A derivatives with reactive Michael acceptor groups at C-2 was created to explore how the compound interacts with the receptor. Most of these derivatives retained high affinity for KOR, and some also bound to the μ-opioid receptor (MOR). None showed wash-resistant irreversible binding. Using the KOR crystal structure, mutagenesis data, and other methods, the researchers identified possible ways the new compounds interact with both KOR and MOR.

DOI: 10.1016/j.ejmech.2014.07.077 Full text Michael acceptor-type ligands Molecular modeling

Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands.

Bioorganic & medicinal chemistry letters May 15, 2013 Prabhakar R Polepally, Kate White, Eyal Vardy et al. 24 citations

Salvinorin A, the active ingredient in the hallucinogenic plant Salvia divinorum, is nature's most potent hallucinogen and selectively activates the κ-opioid receptor. To explore how these compounds bind to specific receptors, researchers synthesized a series of dicarboxylic ester derivatives of salvinorin A and tested their binding affinity at κ-, δ-, and μ-opioid receptors. Most of the new compounds showed high affinity for the κ-opioid receptor. The methyl malonyl derivative 4 had the strongest binding, with a Ki of 2 nM, while analogues 5, 7, and 14 also exhibited significant affinity, with Ki values of 21, 36, and 39 nM respectively. These findings provide insights into brain chemistry and ligand-receptor interactions.

DOI: 10.1016/j.bmcl.2013.03.111 Full text Salvinorin a Hallucinogen Derivatives One particular compound +11