TY - JOUR

T1 - Amides from Piper capense with CNS activity

T2 - a preliminary SAR analysis

AU - Pedersen, Mikael Egebjerg

AU - Metzler, Bjørn

AU - Stafford, Gary Ivan

AU - van Staden, Johannes

AU - Jäger, Anna Katharina

AU - Rasmussen, Hasse Bonde

N1 - Keywords: Piper capense; piperine; GABA; benzodiazepine; epilepsy; multi target effect

PY - 2009

Y1 - 2009

N2 - 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 GABA(A) receptor (IC(50) 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.

AB - 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 GABA(A) receptor (IC(50) 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.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.3390/molecules14093833

DO - 10.3390/molecules14093833

M3 - Journal article

C2 - 19783959

VL - 14

SP - 3833

EP - 3843

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 9

ER -