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Amides from Piper capense with CNS activity - a preliminary SAR analysis.
Mikael E Pedersen1, Bjørn Metzler, Gary I Stafford
1Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. hbr@farma.ku.dk
Molecules (Basel, Switzerland)
|September 29, 2009
Summary
Piper capense roots contain compounds that interact with the GABA(A) receptor, potentially explaining their traditional use for sleep. Structural features of these amides are crucial for receptor binding and sedative effects.
Area of Science:
- Pharmacology
- Natural Products Chemistry
- Neuroscience
Background:
- Piper capense L.f. (Piperaceae) is a South African traditional remedy for inducing sleep.
- The GABA(A) receptor is a key target for sedative and anxiolytic drugs.
Purpose of the Study:
- To identify compounds from Piper capense with activity at the benzodiazepine site of the GABA(A) receptor.
- To elucidate the structure-activity relationships of isolated amides for GABA(A) receptor binding.
Main Methods:
- Bioassay-guided fractionation of Piper capense root extract.
- In vitro assessment of isolated compounds' affinity for the benzodiazepine site on the GABA(A) receptor.
Main Results:
- Piperine (1) and 4,5-dihydropiperine (2) were isolated from Piper capense roots.
- Both compounds exhibited moderate affinity for the benzodiazepine site on the GABA(A) receptor (IC(50) values of 1.2 mM and 1.0 mM, respectively).
Conclusions:
- The study suggests that specific structural characteristics of amides are essential for binding to the GABA(A) receptor's benzodiazepine site.
- A minimum four-carbon chain, a conjugated double bond adjacent to the amide, and a bulky amine moiety are likely necessary for receptor affinity.
