Siedle Bettina, García-Piñeres Alfonso J, Murillo Renato, Schulte-Mönting Jürgen, Castro Victor, Rüngeler Peter, Klaas Christoph A, Da Costa Fernando B, Kisiel Wanda, Merfort Irmgard
Institut für Pharmazeutische Wissenschaften, Lehrstuhl für Pharmazeutische Biologie, Universität Freiburg, 79104 Freiburg, Germany.
J Med Chem. 2004 Nov 18;47(24):6042-54. doi: 10.1021/jm049937r.
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.
倍半萜内酯（SLs）是菊科多种传统药用植物的活性成分。已知它们在不同的炎症模型中具有相当强的抗炎活性。它们可能通过使p65亚基DNA结合域中的半胱氨酸38烷基化来抑制转录因子NF-κB。在此，我们研究了一组代表6个结构组的103种不同倍半萜内酯（44种吉马烷型内酯、16种海链藻型内酯、22种愈创木型内酯、9种假愈创木型内酯、2种次cretenolides、10种桉叶烷型内酯）的NF-κB抑制特性，并将所得的IC(100)值用于定量构效关系（QSAR）研究。针对整个数据集以及不同结构类别的子集，讨论了对抑制效力重要的特性。
