Cytotoxic Arylnaphthalide Lignan
Glycosides from the Aerial Parts of
Phyllanthus taxodiifolius
Table 1 1H-and 13C-NMR data of compound 1 in CDCl3
Position
dHa
dCb
1
±
136.42 (C)
1
1
1
Patoomratana Tuchinda , Anawat Kumkao , Manat Pohmakotr ,
1
2
2
3
3
a
a
a
±
130.76, 130.70* (C)
119.13 (C)
2
3
1
Samaisukh Sophasan , Thawatchai Santisuk , Vichai Reutrakul
±
±
169.74 (C)
±
130.81 (C)
Abstract
5.557, 5.556* (d each, 15, Ha),
67.28 (CH2)
5
±
±
.424, 5.418* (d each, 15, Hb)
The arylnaphthalide lignan glycosides, taxodiifoloside (1), cleis-
tanthoside A (2), cleistanthin A (3) and cleistanthin A methyl
ether (4), together with a triterpene, glochidone (5), have been
isolated from the aerial parts of Phyllanthus taxodiifolius. The
structures were established using spectral and chemical meth-
ods. Compounds 3 and 4, as well as the derivatives 2a and 3a ex-
hibited potent cytotoxic activities with GI values in the range of
4
143.72 (C)
4a
5
126.86 (C)
7.932, 7.927* (s each)
101.52 (CH)
151.95 (C)
6
±
7
±
150.29 (C)
8
7.08 (s)
106.21 (CH)
128.32 (C)
1
¢
±
50
±
7
±9
2¢
6.84, 6.82* (d each, 1.6)
±
110.71, 110.61* (CH)
147.53 (C)
10 ±10 M in five cultured mammalian cancer cell lines while
3
¢ and 4¢
the new compound 1 showed moderate activity (GI in the order
50
of 10±6 M). Compounds 2 and 5 were inactive in all tested cell
5¢
6.96 (d, 8.0)
108.19 (CH)
123.61, 123.50* (CH)
101.22 (CH2)
6
7
¢
¢
6.79 (dd, 8.0, 1.6)
6.099, 6.097* (d each, 1.4, Ha),
lines.
6
.055, 6.053* (d each, 1.4, Hb)
Supporting information available online at
1
2
3
4
¢¢
¢¢
¢¢
¢¢
4.996, 4.993* (d each, 7.0)
3.937, 3.934* (dd each, 8.3, 7.0)
3.43 (t, 8.3)
103.27 (CH)
80.99, 80.92* (CH)
83.08 (CH)
3.46 (obsc.)
79.56 (CH)
Phyllanthus taxodiifolius Beille (Euphorbiaceae), a shrub found in
the central and Northeastern parts of Thailand [1], is used in Thai
traditional medicine as a diuretic. In our ongoing search for an-
ticancer agents from plants, an investigation of the cytotoxic
EtOAc fraction obtained from the partitioning of the crude
MeOH extract of the aerial parts of this plant has led to the isola-
tion of a new arylnaphthalide lignan glycoside, taxodiifoloside
5¢¢
4.037, 4.034*
62.54 (CH2)
(
3
dd each, 12.1, 4.6, Ha), 3.132,
.131* (dd each, 12.1, 8.8, Hb)
1
2
3
¢¢¢
4.68 (d, 7.6)
105.91, 105.87* (CH)
75.32 (CH)
¢¢¢
¢¢¢
3.48 (dd, 9.1, 7.6)
3.64 (t, 9.1)
75.74 (CH)
6
0
4¢¢¢
3.40 (t, 9.1)
69.61 (CH)
5
6
¢¢¢
¢¢¢
3.51 (ddd, 9.1, 4.7, 2.0)
74.76 (CH)
(1), along with three known arylnaphthalide lignan glycosides,
4.38 (dd, 12.3, 4.7, Ha), 4.09
(obsc., Hb)
63.06 (CH2)
cleistanthoside A (2) [2], cleistanthin A (3) [3], [4], [5], cleistan-
thin A methyl ether (4) [3], [4] and a known triterpene, glochi-
done (5) [6], [7]. Compound 4, previously prepared from natural
6-OMe
7-OMe
4.11 (s)
56.53 (CH
55.81 (CH
60.78 (CH
3
3
3
)
)
)
3.81 (s)
3
4
6
6
¢¢-OMe
3.74 (s)
3, was isolated for the first time as a natural product. NMR as-
¢¢-OMe
3.47 (s)
58.23 (CH3)
signments of 1 are reported (Table 1) while the revised data of
other glycosides are included in the Supporting Information [8].
Both natural and modified compounds 1, 2, 2a, 3a, 4 and 5 were
evaluated for cytotoxic effects against five cultured mammalian
cancer cell lines for the first time.
¢¢¢-OCOMe
¢¢¢-OCOMe
1.79 (s)
20.20 (CH3)
±
171.54 (C = O)
OH
4.69 (br), 3.34 (br), 3.29 (br)
±
a
Recorded at 500 MHz; chemical shift given in ppm using TMS as internal reference; multipli-
cities and J values (Hz) are given in parentheses; obsc. = obscured signal.
b
1
3 C
Recorded at 125 MHz; chemical shift given in ppm using CDCl signal at d = 77.00 as re-
Taxodiifoloside (1) (C H O ) displayed typical H-NMR signals
3
6
40 17
ference.
of a substituted arylnaphthalene nucleus and a disaccharide por-
* A doubling of signals was observed due to restricted rotation.
tion (Table 1). The doubling of some signals, due to restricted ro-
Affiliation: 1 Department of Chemistry, Faculty of Science, Mahidol University,
tation around the aryl-naphthalene bond [9], is indicated by an
Bangkok, Thailand ´ Department of Physiology, Faculty of Science, Mahidol asterik (*). The presence of signals corresponding to two aromat-
2
3
University, Bangkok, Thailand ´ The Forest Herbarium, Royal Forest Depart-
ic protons, a 1,3,4-trisubstituted phenyl moiety, a lactone methy-
lene, a methylenedioxy group and two aromatic methoxy groups
ment, Bangkok, Thailand
Correspondence: Dr. Patoomratana Tuchinda ´ Department of Chemistry ´ Fa- suggested that 1 was a diphyllin analogue. The sugars in the dis-
culty of Science ´ Mahidol University ´ Rama 6 Road ´ Bangkok 10400 ´ Thailand ´
Fax: +66-02-3547151 ´ E-mail: scptc@mahidol.ac.th
accharide unit were identified as 3,4-di-O-methyl-b-
nose and 6-acetoxy-b- -glucopyranose by analyses of the J val-
ues, 13C-NMR (Table 1) and 2D-NMR data (Table 1 in Supporting
D
-xylopyra-
D
Received: May 30, 2005 ´ Accepted: August 19, 2000
Bibliography: Planta Med 2006; 72: 60±62 ´ ꢀ Georg Thieme Verlag KG Information). The locations of the methoxy groups at C-3¢¢, C-4¢¢
Stuttgart ´ New York ´ DOI 10.1055/s-2005-873141 ´ Published online October
and the acetoxy group at C-6¢¢¢ were confirmed with HMBC corre-
lations. The connectivities of the two sugars and to the diphyllin
14, 2005 ´ ISSN 0032-0943