Amides from Piper capense with CNS Activity – A Preliminary SAR Analysis

Molecules

Mikael E. Pedersen¹  Bjørn Metzler¹  Gary I. Stafford¹  Johannes Van Staden¹  Anna K. Jäger¹ 

[1] ¹Department of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark ²Research Centre for Plant Growth and Development, School of Biological and Conservation Sciences, University of KwaZulu-Natal, Pietermaritzburg, Private Bag X01, Scottsville 3209, South Africa

关键词: Piper capense;    piperine;    GABA;    benzodiazepine;    epilepsy;    multi target effect;   

DOI  :  10.3390/molecules14093833

来源: mdpi

【 摘 要 】

Piper capense L.f. (Piperaceae) is used traditionally in South Africa as a sleep inducing remedy. Bioassay-guided fractionation of the roots of P. capense led to the isolation of piperine (1) and 4,5-dihydropiperine (2), which showed moderate affinity for the benzodiazepine site on the GABAA receptor (IC₅₀ values of 1.2 mM and 1.0 mM, respectively). The present study suggests that strict structural properties of the amides are essential for affinity. Taken together, these observations suggest that the carbon chain must contain not less than four carbons, and that a conjugated double bond, adjacent to the amide group, is necessary for binding to the receptor and that the amine part should be bulky.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.