Sesquiterpene lactones from Montanoa hibiscifolia that inhibit the transcription factor NF-kappa B.
The reinvestigation of the aerial parts of Montanoa hibiscifolia afforded four new eudesmanolides (1-4), three of them with a rare endoperoxide structural element and the fourth with a rare carbonyl function. It also afforded three unusual montabibisciolides (5-7), two (5 and 7) of which are new natural compounds. Additionally, seven germacrolides (8-10 and 12-15) and one melampolide (11) could be isolated, including two new germacrolides (8 and 9). Their structures were elucidated using 1D and 2D NMR measurement as well as ESI, CIMS, and HRMS analyses. Low-energy conformations were obtained by molecular mechanics calculations. The (13)C NMR data of five compounds are reported for the first time. Six sesquiterpene lactones (4, 6, 10, 11, 12, and 14) were investigated for their inhibitory activity on DNA binding of the transcription factor NF-kappa B using Jurkat T cells as well as RAW 264.7 cells. Besides the alpha-methylene-gamma-butyrolactone moiety the epoxy group in the acyl residue might take part in the NF-kappa B inhibitory activity of sesquiterpene lactones.
Müller
Stefan
S
Institut für Pharmazeutische Wissenschaften, Lehrstuhl für Pharmazeutische Biologie, Universität Freiburg, 79104 Freiburg, Germany.
Murillo
Renato
R
Castro
Victor
V
Brecht
Volker
V
Merfort
Irmgard
I
D003364:Costa Rica; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019169:Jurkat Cells; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008968:Molecular Conformation; D015394:Molecular Structure; D035924:Montanoa / Q000737:chemistry*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007783:Lactones; D016328:NF-kappa B; D012717:Sesquiterpenes