Flavonol glycosides from Centaurea furfuracea. Antiplasmodial and cytotoxic activities

Full text of DOI:10.1007/s10600-007-0117-y

Chemistry of Natural Compounds, Vol. 43, No. 3, 2007
FLAVONOL GLYCOSIDES FROM entaurea furfuracea.
ANTIPLASMODIAL AND CYTOTOXIC ACTIVITIES
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S. Akkal, F. Benayache, K. Medjroubi, and F. Tillequin
UDC 547.972
Many species of the genus Centaurea (Asteraceae) have been used in folk medcine since ancient times. These plants
are generally rich in flavonoids and sesquiterpene lactones, which are the main constituents responsible for biological activity
[1–6]. In a previous study, we described 10 flavonoids from Centaurea furfuracea [6, 7].
C. furfuracea Coss. et kral. was collected at the beginning of April 1992 in the region of Biskra and was identified by
Dr. M. Kaabech from the University of Setif Algeria on the basis of Quezel and Santa [8]. A voucher specimen has been
deposited in the herbarium of the Museum National d′Histoire Naturelle, Paris, France.
Powdered dried aerial parts from C. furfuracea were extracted with MeOH. The MeOH extract was concentrated. The
concentrate was taken up with CHCl and n-BuOH. The latter, by preparative PC on Whatman 3MM paper using 15% AcOH
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and BAW (n-BuOH–AcOH–H O 4:1:5), upper phase as solvents, gave compounds 1 and 2.
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Purification ofeach compoundsfor spectralanalysiswascarriedoutusingSephadexLH-20;column elutedwith MeOH;
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prior to UV, MS, and H NMR spectral analysis, color reaction procedure; hydrolysis of the glycosides (0.1 N HCl, 2 h) (Mabry
et al.) [9, 10].
Ultraviolet and visible absorption spectra weredeterminedwith a Perkin–Elmer Lamda 17UV/VIS spectrophotometer.
Absorption maxima were obtained in methanol. Spectra shifts were recorded after adding a standard solution of sodium
hydroxide, aluminium chloride, hydrochloric acid, and crystals of sodium acetate.
Compounds 1 and 2 bytreatment with 2 N HCl (2 h, 100°C) gave glucuronic acid and the aglycone identified as Me-3
kaempferol (isokaempferide).
The structures were established on the basis of NMR spectroscopic experiments and by comparison of the NMR data.
Compound 2 was reported previously from another species of Centaurea [11], and from C. furfuracea for the first time. The
glycoside 1 is new for the genus Centaurea.
The UV spectra of 1 were typical of flavone or 3-O substituted flavonol. After adding 2 N NaOH, it showed no band
shift between 320 and 335 nm, whereas band II was not shifted by adding NaOAc. This was in agreement with substitution
of the 7-hydroxyl group [12]. The shift of band I in the sodium hydroxide spectrum of compound 1 indicated a bathochromic
shift with increased intensity and supported the presence of a free 4′-hydroxyl group. The negative Electrospray MS of
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compound 1 exhibited a quasi-molecular ion [M-H] at m/z 489, suggestive of the empirical formula C H O . The H NMR
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spectrum of compound 1 obtained in CD OD and the AA′BB′ system consists of two proton doublets (J = 8.4 Hz) at δ 7.94 and
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.90 typical of a para-substituted B ring of flavonoid. Two further coupled doublets (J = 2 Hz) at δ 6.80 and 6.55 indicated
the presence of the meta-related H-6 and H-8 ring A protons. The presence of two methoxyl groups was shown by two 3H
singlets at δ 3.85 and 3.92. The presence of a sugar moiety was revealed by the anomeric proton resonance (δ 5.30, d,
J = 8 Hz). Therefore, 1 was identified as isokaempferide 7-O-methylglucuronide. The other isolated compound gave the
isokaempferide 7-O-glucuronide (2).
Isokaempferide 7-O-Methylglucuronide (1). C H O , UV/Vis(MeOH): λ 272, 333nm; NaOH: 252, 274, 385;
max
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AlCl : 279, 357; AlCl /HCl: 280, 350; + NaOAc 270, 390 nm. H NMR (300 MHz, CD OD, J/Hz): 7.94 (2H, d, J = 8.4, H-2′,
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H-6′), 6.90 (2H, d, J = 8.4, H-3′, H-5′), 6.80 (1H, d, J = 2, H-8), 6.55 (1H, d, J = 2, H-6), 3.92 (3H, s, COOMe), 3.85 (3H, s,
OMe-3), 5.30 (1H, d, J = 8, anomeric proton ofglucuronic methylester H-1′′), 4.23 (1H, d, J = 10, H-5′′ CH-COOMe), 3.30–3.70
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) Department of Chemistry, University of Mentouri Constantine 25000 Constantine, Algeria, fax + 213 31 62 49 12;
e-mail: salah4dz@yahoo.fr; 2) Laboratoire de Pharmacognosie, URA au CNRS 8638, Faculte de Pharmacie, Universite Rene
Descartes Paris V, Paris, France. Published in Khimiya Prirodnykh Soedinenii, No. 3, pp. 265-266, May-June, 2007. Original
article submitted March 29, 2006.
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009-3130/07/4303-0319 2007 Springer Science+Business Media, Inc.
319

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3H, m, H-2′′, H-3′′, H-4′′). ES-MS negative ion mode m/z: 489 [M-H] , 299 [M-190(Megluc) -H] ; ES-MS positive ion mode
(
+
+
m/z: 491 [M+H ] , 301 [M-190(Megluc) +H] .
Isokaempferide 7-O-Glucuronide (2). C H O , UV/Vis (MeOH): λ 267, 345; NaOH: 252, 270, 395; AlCl3:
max
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74, 356, 399; AlCl /HCl: 273, 351, 398 nm. H NMR (300 MHz, CD OD, J/Hz): 7.95 (2H, d, J = 8.4, H-2′, H-6′), 6.96 (2H,
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d, J = 8.4, H-3′, H-5′), 6.85 (1H, d, J = 2, H-8), 6.56 (1H, d, J = 2, H-6), 3.81 (3H, s, OMe-3), 5.50 (1H, d, J = 8, anomeric
proton of glucuronic acid H-1′′) 4.25 (1H, d, J = 10, H-5′′ CH-COOH), 3.25–3.75 (3H, m, H-2′′, H-3′′, H-4′′, H) ES-MS positive
+
+
ion mode m/z: 477 [M+H] , 301 [M-176(gluc) +H] .
Antiplasmodial,Cytotoxic Activities. Antiplasmodial andcytotoxicactivitieswereevaluatedaccordingtoestablished
protocols [13, 14].
Tested on Plasmodium falciparum, the chloroform extract exhibited antiparasitic activity (IC50 7.94 µg/mL). On KB
cells, it showed cytotoxic activity with a growth inhibition of 90% at 10 µg/mL and 26% at 1 µg/mL.
ACKNOWLEDGMENT
We are thankful to Dr. M. Kaabeche (Department of Biology, University of Setif, Algeria) for identifying the plant
material. Thanks are due to Prof. Thierry Fevenet, UCSN, UPR 2031 CNRS, Gif-sur Yvette cedex France for his assistance in
studying the biological activities of this plant.
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