Extracellular Signal-Regulated Kinases (ERK) Inhibitors from Aristolochia yunnanensis.
Six new sesquiterpenoids, aristoyunnolins A-F (1-6), an artifact of isolation [7-O-ethyl madolin W (7)], and 12 known analogues were isolated from stems of Aristolochia yunnanensis. The structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds 2, 3, 5-7, 9, 14, and 17 were determined by the modified Mosher's method and CD analysis. Compounds 1-19 were screened using a bioassay system designed to evaluate the effect on mitogen-activated protein kinases (MAPKs) signaling pathways. Among three MAPKs (ERK1/2, JNK, and p38), compounds 1, 4, 10-13, 16, 18, and 19 exhibited selective inhibition of the phosphorylation of ERK1/2. Compounds 16 and 19 were more active than the positive control PD98059, a known inhibitor of the ERK1/2 signaling pathway.
T10 T11 T12 T13 T14 T1 T2 T3 T4 T5 T6 T7 T8 T9
GENE-N GENE-N GENE-N GENE-N GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-N GENE-N GENE-N GENE-N GENE-N
p38 ERK1/2 ERK1/2 Extracellular Signal-Regulated Kinases ERK aristoyunnolins A-F PD98059 7-O-ethyl madolin W sesquiterpenoids mitogen-activated protein kinases MAPKs MAPKs ERK1/2 JNK