Unusual cycloartane glycosides from Astragalus eremophilus
Angela Perrone
a
, Milena Masullo
a
, Carla Bassarello
a
, Elena Bloise
a
, Arafa Hamed
b
, Patrizia Nigro
a
,
Cosimo Pizza
a
, Sonia Piacente
a
,
*
a
Dipartimento di Scienze Farmaceutiche, Universita
`
degli Studi di Salerno, via Ponte Don Melillo, 84084 Fisciano (SA), Italy
b
Faculty of Science, South Valley University, 81528 Aswan, Egypt
article info
Article history:
Received 18 December 2007
Received in revised form 5 March 2008
Accepted 19 March 2008
Available online 22 March 2008
Keywords:
Astragalus eremophilus
Cycloartane glycosides
Cytotoxic activity
NMR
abstract
Eleven new cycloartane-type glycosides, named eremophilosides A–K have been isolated from the aerial
parts of Astragalus eremophilus. Their structures were elucidated by MS and NMR experiments and the
relative configurational analysis of eremophilosides C and D was carried out on the basis of the recently
reported J-based method. Additionally, the cytotoxic activity of these compounds in MCF7 and U937 cell
lines was evaluated. All tested compounds, except eremophilosides B, C, and J were found to inhibit
slightly the growth (controlling the cell cycle) and/or to induce death processes in U937 cell line, the
most susceptible cell line. Eremophilosides A and K resulted the most effective to induce cell death, the
first by necrosis while the latter by apoptosis.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Astragalus L., the largest genus in the family Leguminosae,
comprises 2000 species distributed mainly in the northern tem-
perate regions and tropical African mountains and in particular it is
represented by 32 species indigenous to Egypt.
1,2
The roots of various Astragalus species represent very old and
well-known drugs in traditional medicine for the treatment of
nephritis, diabetes, leukemia, uterine cancer and as antiperspirant,
diuretic, and tonic.
3
Astragalus species showed interesting phar-
macological properties including hepatoprotective, immunosti-
mulant, and antiviral activities.
4,5
Anti-inflammatory, analgesic,
sedative, and cardiovascular activities are also reported.
4,6
Astragalus species are known to be rich in two major classes of
biologically active compounds, polysaccharides and saponins.
3
Astragalus polysaccharides are reported to have anticancer and
immunostimulating effects.
4
The latter group of constituents is the
most widely studied secondary metabolites: previous study on
Astragalus saponins have reported the presence of cycloartane- and
oleanene-type glycosides, which were found to exert biological
activities.
4,5
The immunostimulant effects of several cycloartane
glycosides on macrophage activation and expression of in-
flammatory cytokines were investigated.
7–9
Recently, cycloartanes
from Astragalus species have attracted interest because of their
leishmanicidal
10
and antibacterial activities.
7
Phytochemical studies on several Egyptian Astragalus species
have resulted in the isolation of a series of cycloartane-type sapo-
nins.
11–20
Some of these glycosides have shown interesting anti-
tumor activity against human tumor cell lines and also AIDS
antiviral activity,
18
others have been reported to act as modulators
of lymphocyte proliferation.
15,16
Cycloartane glycosides have been reported for their cytotoxic
activity on several cancer lines including solid tumor (HepG2),
blood tumor (HL-60), and drug resistant tumor (R-HepG2).
21
Moreover cancer chemopreventive effects of natural and semi-
synthetic cycloartane-type and related triterpenoids have been
reported.
22
On the basis of interesting activities reported for many Astra-
galus species and for cycloartane glycosides and as a part of our
ongoing research of new bioactive compounds from Egyptian
species, we have investigated the aerial parts of Astragalus eremo-
philus Boiss. (Leguminosae). This paper reports the isolation of
eleven new cycloartane-type glycosides, named eremophilosides
A–K (1–11). Their structures were elucidated by extensive spec-
troscopic methods including 1D- (
1
H,
13
C, and TOCSY) and 2D-NMR
(DQF-COSY, HSQC, HMBC, HETLOC, and ROESY) experiments as well
as ESIMS analysis.
Since cycloartane glycosides have shown to possess cytotoxic
activity,
22
we have evaluated the potential effect of compounds
1–11 on tumor cell growth in MCF7 (breast carcinoma) and U937
(monocytic leukemia) cell lines.
*
Corresponding author. Tel.: þ39 089 969763; fax: þ39 089 969602.
E-mail address: piacente@unisa.it (S. Piacente).
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Tetrahedron 64 (2008) 5061–5071
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.069