Abstract
Cytotoxicity-guided fractionation of the methanol soluble part of the dichloromethane extract of the leaves of Warionia saharae led to the isolation of the two new guaianolide-type sesquiterpene lactones, 5αH -3β ,4β -epoxy-14-oxo-guaia-1(10),11(13)-dien-6α ,12-olide (1 ), 5α
H -2β ,4β -epoxy-3α -hydroxy-guaia-1(10),11(13)-dien-6α ,12-olide (6 ), and the new eudesmane type sesquiterpene 1β ,6α -dihydroxycostic acid (4 ). In addition, the known sesquiterpene lactones 5α
H -2β -hydroxyguaia-3(4),10(14),11(13)-trien-6α ,12-olide (2 ), reynosin (3 ), 5α
H -1α ,10α :3α ,4α -diepoxyguaia-11(13)-en-6α ,12-olide (5 ), and dehydroleucodin (7 ) were isolated together with the known flavone hispidulin. Cytotoxicity testing of the sesquiterpene lactones against the KB cancer cell line (ATCC CCL17) revealed IC50 values of 3.5 (1 ), 2.6 (2 ), 2.7 (3 ), 4.3 (5 ), 3.6 (6 ), and 1.3 (7 ) μg/mL. Compound 4 was not active up to 20 μg/mL.
References
1 Bellkhadar J. La pharmacopée marocaine traditionelle; Médicine arabe ancienne et savoirs populaires. IBIS Press 1997;: p. 213
2
Ramaut J L, Hofimger M, Dimbi R, Corvisier M, Lewalle J.
Main constituents of the essential oil of Warionia saharae
.
Chromatographia.
1985;
20
193
3
Hilmi F, Sticher O, Heilmann J.
New cytotoxic 6,7-cis and 6,7-trans configured guaianolides from Warionia saharae
.
Journal of Natural Products.
2002;
65
523-6
4
Sigstad E E, Catalan C AN, Gutierrez A B, Diaz J G, Goedken V L, Herz W.
Guaianolides and germacranolides from Stevia grisebachiana
.
Phytochemistry.
1991;
30
1933-40
5
Sosa V E, Oberti J C, Gil R R, Ruveda E A.
10-Epideoxycumambrin B and other constituents of Stevia yaconensis var. subeglandulosa
.
Phytochemistry.
1988;
28
1925-9
6
Geissman T A, Griffin T S.
Sesquiterpene lactones of Artemisia carruthii
.
Phytochemistry.
1972;
11
833-5
7
Seaman F C, Bencsath A.
A eudesmane acid from Montanoa speciosa
.
Phytochemistry.
1985;
24
607-8
8
Rao K V, Alvarez F M.
Antibiotic principle of Eupatorium capillifolium
.
Journal of Natural Products.
1981;
44
252-6
9
Todorova M N, Tsankova E T, Taskova R M, Peev D R.
Terpenoids from Achillea clusiana
.
Zeitschrift für Naturforschung.
1999;
54c
1011-5
10
Yoshioka H, Renold W, Fischer N H, Higo A, Mabry T J.
Sesquiterpene lactones from Ambrosia confertiflora (Compositae).
Phytochemistry.
1970;
9
823-32
11
Ando M, Yoshimura H.
Syntheses of four possible diastereomeres of Bohlmann's structure of isoepoxestafiatin. The stereochemical assignment of isoepoxyestafiatin.
Journal of Organic Chemistry.
1993;
58
4127-31
12
Ilidrissi A, Berrada M, Holeman M, Gorrichon L.
Mésatlantines, nouvelles lactones sesquiterpéniques d’Artemisia mesatlantica
.
Fitoterapia,.
1991;
62
107-13
13
Bohlmann F, Zdero C.
Zwei neue Sesquiterpen-Lactone aus Lidbeckia pectinata Ber. and Pentzia elegans DC.
Tetrahedron Letters.
1972;
7
621-4
14
De Heluani C S, De Lampasona M P, Catalàn C AN, Goedken V L, Gutiérrez A B, Herz W.
Guaianolides, Heliangolides and other constituents from Stevia alpina
.
Phytochemistry.
1989;
28
1931-5
15
Hase T, Ohtani K, Kasai R, Yamasaki K, Picheansoonthon C.
Revised structure for hortensin, a flavonoid from Millingtonia hortensis
.
Phytochemistry.
1995;
40
287-90
16
Heilmann J, Wasescha M R, Schmidt T J.
The influence of glutathione and cysteine levels on the cytotoxicity of helenanolide type sesquiterpene lactones against KB cells.
Bioorganic and Medicinal Chemistry.
2001;
9
2189-94
PD Dr. Jörg Heilmann
Swiss Federal Institute of Technology (ETH) Zurich
Institute of Pharmaceutical Sciences
Winterthurerstr. 190
8057 Zürich
Switzerland
Telefon: +41-1-6356049
Fax: +41-1-6356882
eMail: joerg.heilmann@pharma.anbi.ethz.ch