Quantitative structure-activity relationship of sesquiterpene lactones as inhibitors of the transcription factor NF-kappaB.
Sesquiterpene lactones (SLs) are the active compounds of a variety of traditionally used medicinal plants from the Asteraceae family. They are known to possess a considerable antiinflammatory activity in different inflammation models. They inhibit the transcription factor NF-kappaB probably by alkylating cysteine38 in the DNA binding domain of the p65 subunit. Here we investigate a set of 103 different sesquiterpene lactones representing 6 structural groups (44 germacranolides, 16 heliangolides, 22 guaianolides, 9 pseudoguaianolides, 2 hypocretenolides, 10 eudesmanolides) for their NF-kappaB inhibiting properties and the resulting IC(100)-values were submitted to a QSAR study. Properties important for the inhibition potency are discussed for the whole data set and for subsets of the different structural classes.
Siedle
Bettina
B
Institut für Pharmazeutische Wissenschaften, Lehrstuhl für Pharmazeutische Biologie, Universität Freiburg, 79104 Freiburg, Germany.
García-Piñeres
Alfonso J
AJ
Murillo
Renato
R
Schulte-Mönting
Jürgen
J
Castro
Victor
V
Rüngeler
Peter
P
Klaas
Christoph A
CA
Da Costa
Fernando B
FB
Kisiel
Wanda
W
Merfort
Irmgard
I
D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D019169:Jurkat Cells; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D012717:Sesquiterpenes / Q000737:chemistry* / Q000494:pharmacology
D007783:Lactones; D016328:NF-kappa B; D012717:Sesquiterpenes