New cytotoxic 6,7-cis and 6,7-trans configured guaianolides from Warionia saharae.
Using cytotoxicity against the KB cancer cell line (ATCC CCL17) as a lead, bioactivity-guided fractionation of the MeOH-soluble part of the DCM extract of Warionia saharae leaves led to the isolation of six new cytotoxic guaianolide type sesquiterpene lactones (1-6). Besides two guaianolides showing the common 6,7-trans fused lactone ring (3 and 4), four compounds exhibiting the more rare 6,7-cis configuration (1,2 and 5,6) were also isolated. Compounds 1, 2, 5, and 6 showed an unprecedented ether bridge between C-2 and C-4. The structures were deduced from extensive 1D and 2D NMR spectroscopy ((1)H, (13)C, DQF-COSY, HSQC, HMBC, ROESY), as well as mass spectrometry (EI and HR-MALDI). Cytotoxicity testing against the KB cancer cell line revealed IC(50) values of 1.0 (1), 4.5 (2), 1.7 (3), 2.0 (4), 3.3 (5), and 5.5 (6) microg/mL.
Hilmi
Fatima
F
Department of Applied BioSciences, Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Sticher
Otto
O
Heilmann
Jörg
J
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019659:Asteraceae / Q000737:chemistry*; D005260:Female; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D007624:KB Cells; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D009018:Morocco; D019906:Nuclear Magnetic Resonance, Biomolecular; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured / Q000187:drug effects; D002583:Uterine Cervical Neoplasms
D000972:Antineoplastic Agents, Phytogenic; D007783:Lactones; D012717:Sesquiterpenes