Sesquiterpenes from Neurolaena lobata and their antiproliferative and anti-inflammatory activities.
Five new sesquiterpenes, neurolobatin A (1), neurolobatin B (2), 5β-hydroxy-8β-isovaleroyloxy-9α-hydroxycalyculatolide (3), 3-epi-desacetylisovaleroylheliangine (4), and 3β-acetoxy-8β-isovaleroyloxyreynosin (5), were isolated from the aerial parts of Neurolaena lobata. The structures were established by means of a combined spectroscopic data analysis, including ESIMS, APCI-MS, and 1D- and 2D-NMR techniques. Neurolobatin A (1) and B (2) are unusual isomeric seco-germacranolide sesquiterpenes with a bicyclic acetal moiety, compounds 3 and 4 are unsaturated epoxy-germacranolide esters, and compound 5 is the first eudesmanolide isolated from the genus Neurolaena. The isolated compounds (1-5) were shown to have noteworthy antiproliferative activities against human tumor cell lines (A2780, A431, HeLa, and MCF7). The anti-inflammatory effects of 1-5, evaluated in vitro using LPS- and TNF-α-induced IL-8 expression inhibitory assays, revealed that all these compounds strongly down-regulated the LPS-induced production of IL-8 protein, with neurolobatin B (2) and 3-epi-desacetylisovaleroylheliangine (4) being the most effective.
Department of Pharmacognosy, University of Szeged , Eotvos Str. 6, H-6720 Szeged, Hungary.
Ildikó
I
Lajter
Andrea
A
Vasas
Zoltán
Z
Béni
Peter
P
Forgo
Markus
M
Binder
Valery
V
Bochkov
István
I
Zupkó
Georg
G
Krupitza
Richard
R
Frisch
Brigitte
B
Kopp
Judit
J
Hohmann
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006166:Guatemala; D006367:HeLa Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D045788:Sesquiterpenes, Germacrane / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D016209:Interleukin-8; D008070:Lipopolysaccharides; D045788:Sesquiterpenes, Germacrane; D014409:Tumor Necrosis Factor-alpha; C432449:germacranolide