834
Vol. 57, No. 8
and C-28), 60.9 (CH3, 7-OMe), 26.2 (CH2, C-16), 21.6 (CH2, C-11), 25.9
and 25.8 (CH3, C-15 and C-20), 18.2 and 17.9 (CH3, C-14 and C-19).
3,6-Di-O-4-methylbenzyl a-Mangostin (13): Yellow fine needles, mp
98—100 °C; EI-MS C40H42O6, m/z: 617.1 [MꢀH]ꢀ; 1H-NMR (300 MHz,
CDCl3) d: 13.50 (1H, s, 1-OH), 7.32 and 7.22 (8H, m, Ar-H), 6.74 (1H, s,
H-5), 6.32 (1H, s, H-4), 5.26 (2H, t, Jꢁ6.6 Hz, H-12 and H-17), 5.13 and
5.09 (each 2H, s, H2-21 and 22), 4.13 (2H, d, Jꢁ6.9 Hz, H2-16), 3.81 (3H, s,
7-OMe), 3.39 (2H, d, Jꢁ6.6 Hz, H2-11), 2.37 and 2.36 (each 3H, s, H3-25
and H3-32), 1.85, 1.71, 1.68 and 1.67 (each 3H, s, H3-14, H3-15, H3-19 and
H3-20); 13C-NMR (75 MHz, CDCl3) d: 182.0 (C, C-9), 162.4 (C, C-3), 159.9
(C, C-1), 157.0 (C, C-6), 155.1 (C, C-10a), 155.0 (C, C-4a), 144.2 (C, C-7),
138.2 and 137.8 (C, C-22 and C-29), 137.3 (C, C-8), 131.5 and 131.7 (C, C-
18 and C-13), 133.3, 132.7 (C, C-25 and C-32), 129.4, 129.3, 127.4 and
127.3 (each CHꢃ2, C-23, C-24, C-26, C-27, C-30, C-31, C-33, C-34), 123.3
and 122.4 (CH, C-12 and C-17), 112.2 (C, C-8a), 111.8 (C, C-2), 104.1 (C,
C-9a), 99.4 (CH, C-5), 89.8 (CH, C-4), 70.6 and 70.2 (CH2, C-21 and C-28),
60.9 (CH3, 7-OMe), 26.2 (CH2, C-16), 25.9 and 25.8 (CH3, C-15 and C-20),
22.7 (CH2, C-11), 21.5 and 21.2 (CH3, 25-CH3 and 32-CH3), 18.2 and 17.9
(CH3, C-14 and C-19).
3,6-Di-O-n-pentyl a-Mangostin (14): Yellow fine needles, mp 135—
138 °C; EI-MS C34H46O6, m/z: 549.3 [MꢀH]ꢀ; 1H-NMR (300 MHz, CDCl3)
d: 13.49 (1H, s, 1-OH), 6.54 (1H, s, H-5), 6.24 (1H, s, H-4), 5.25 (2H, t, Jꢁ
6.6 Hz, H-12 and H-17), 4.12 (2H, d, Jꢁ6.6 Hz, H2-16), 4.02 (4H, m, H2-
21and H2-26), 3.80 (3H, s, 7-OMe), 3.35 (2H, d, Jꢁ6.6 Hz, H2-11), 1.92
(4H, m, H2-22 and H2-27), 1.85, 1.80 (each 3H, s) and 1.68 (6H, s), H3-14,
H3-15, H3-19 and H3-20, 1.50 and 1.41 (each 4H, m, H2-23, H2-24, H2-28
and H2-29), and 0.97 (6H, m, H3-25 and H3-30); 13C-NMR (75 MHz, CDCl3)
d: 182.0 (C, C-9), 162.9 (C, C-3), 159.8 (C, C-1), 157.5 (C, C-6), 155.3 (C,
C-10a), 155.1 (C, C-4a), 144.0 (C, C-7), 137.0 (C, C-8), 131.5 and 131.2 (C,
C-13 and C-18), 123.4 and 122.6 (CH, C-12 and C-17), 111.8 (C, C-8a),
111.4 (C, C-2), 103.8 (C, C-9a), 98.7 (C, C-5), 89.2 (C, C-4), 60.8 (CH3, 7-
OMe), 68.8 and 68.4 (CH2, C-21 and C-26), 26.2 (CH2, C-16), 25.9 and 25.8
(CH3, C-15 and C-20), 28.9, 28.7, 28.3, 28.2, 22.5 and 22.4 (CH2, C-22, C-
23, C-24, C-27, C-28 and C-29), 22.7 (CH2, C-11), 18.2 and 17.8 (CH3, C-
14 and C-19), 14.1 and 14.0 (CH3, C-25 and C-30).
3,6-Di-O-n-butyl a-Mangostin (15): Yellow fine needles; mp 129—
132 °C; EI-MS C32H42O6, m/z: 521.3 [MꢀH]ꢀ; 1H-NMR (300 MHz, CDCl3)
d: 13.49 (1H, s, 1-OH), 6.68 (1H, s, H-5), 6.26 (1H, s, H-4), 5.25 (2H, t, Jꢁ
6.6 Hz, H-12 and H-17), 4.12 (2H, d, Jꢁ6.6 Hz, H2-16), 4.04 (4H, m, H2-21
and H2-25), 3.80 (3H, s, 7-OMe), 3.35 (2H, d, Jꢁ6.6 Hz, H2-11), 1.85, 1.79
(each 3H, s) and 1.68 (6H, s, CH3), H3-14, H3-15, H3-19 and H3-20, 1.90
(4H, m, H2-22 and H2-26), 1.54 (4H, m, H2-23 and H2-27), 1.01 (6H, m, H3-
24 and H3-28); 13C-NMR (75 MHz, CDCl3) d: 182.0 (C, C-9), 162.9 (C, C-
3), 159.8 (C, C-1), 157.5 (C, C-6), 155.3 (C, C-10a), 155.1 (C, C-4a), 144.0
(C, C-7), 137.0 (C, C-8), 131.6 and 131.3 (C, C-13 and C-18), 123.4 and
122.6 (CH, C-12 and C-17), 111.8 (C, C-8a), 111.4 (C, C-2), 103.8 (C, C-
9a), 98.6 (C, C-5), 89.2 (C, C-4), 60.8 (CH3, 7-OMe), 68.5 and 68.1 (CH2,
C-21 and C-25), 26.2 (CH2, C-16), 22.5 (CH2, C-11), 25.9 and 25.8 (CH3,
C-14 and C-19), 18.2 and 17.8 (CH3, C-15 and C-20), 31.2, 31.0, 19.3ꢃ2
(CH2, C-22, C-26, C-23, C-27), 14.1 and 14.0 (C3, C-24 and C-28).
(1H, m, H-22), 4.68 (2H, d, Jꢁ5.1 Hz, H2-21), 4.13 (2H, d, Jꢁ7.1 Hz, H2-
16), 3.80 (3H, s, 7-OMe), 3.35 (2H, d, Jꢁ6.6 Hz, H2-11), 1.85 (6H, s), 1.78
(3H, s), and 1.68 (3H, s), H3-14, H3-15, H3-19 and H3-20; 13C-NMR
(75 MHz, CDCl3) d: 182.0 (C, C-9), 161.5 (C, C-3), 160.6 (C, C-1), 156.0
(C, C-6), 155.3 (C, C-10a), 155.0 (C, C-4a), 144.2 (C, C-7), 137.1 (C, C-8),
135.9 (CH, C-22), 131.6 and 131.4 (C-13 and C-18), 123.4 and 122.5 (C-12
and C-17), 118.5 (CH2, C-23), 111.8 (C, C-8a), 108.3 (C, C-2), 103.8 (C, C-
9a), 99.3 (C, C-5), 93.2 (C, C-4), 69.5 (CH2, C-21), 60.9 (CH3, 7-OMe),
26.2 (CH2, C-16), 21.5 (CH2, C-11), 25.9 and 25.8 (CH3, C-15 and C-20),
18.2 and 17.9 (CH3, C-14 and C-19).
Cytotoxicity Assay The cells for cytotoxicity assays, MCF-7 (human
mammary cancer cells) was obtained from Division of Cancer Treatment
and Diagnosis (NCI, Maryland, U.S.A.) and DLD-1 (human colonic cells)
from ATCC (American Type Culture Collections). The in vitro cytotoxicity
assay was carried out according to the procedures described previously using
SRB18) with 0.01% campothecin or 60 mM resveratrol as positive control.
The absorbance at 492 and 620 nm (reference wavelength) was recorded
using Synergy HT microplate reader (Bio-Tek). All mangostin derivatives
(10—17) were screened at 110 mM concentration by comparison with 22 mM
of 1, 2 and 3 on MTT assay19) using 60 mM resveratrol as positive control.
For the MTT assay, the absorbance was recorded at 570 and 620 nm (refer-
ence wavelength) using Synergy HT microplate reader (Bio-Tek).
Acknowledgements We would very like to thank Dr. Jan Christensen,
KU-Life, for HR-MS measurement. We would like to thank DANIDA for
the award of a postgraduate scholarship to Ly D. Ha financed through the
ENRECA Program.
References
1) Peres V., Nagem T. J., De Oliveira F. F., Phytochemistry, 55, 683—710
(2000).
2) Chen S. X., Wan M., Loh B. N., Planta Med., 62, 381—382 (1996).
3) Pinto M. M., Sousa M. E., Nascimento M. S., Curr. Med. Chem., 12,
2517—2538 (2005).
4) Ee G. C. L., Lim C. K., Rahmat A., Nat. Prod. Sci., 11, 220—224
(2005).
5) Chen L. G., Yang L. L., Wang C. C., Food Chem. Toxicol., 46, 688—
693 (2008).
6) Nakagawa Y., Iinuma M., Naoe T., Nozawa Y., Akao Y., Bioorg. Med.
Chem., 15, 5620—5828 (2007).
7) Mtsumoto K., Akao Y., Kobayashi E., Ohguchi K., Ito T., Tanaka T.,
Iinuma M., Nozawa Y., J. Nat. Prod., 66, 1124—1127 (2003).
8) Matsumoto K., Akao Y., Ohguchi K., Ito T., Tanaka T., Iinuma M.,
Nozawa Y., Bioorg. Med. Chem., 13, 6064—6069 (2005).
9) Suksamrarn S., Komutiban O., Ratananukul P., Chimnoi N., Lartporn-
matulee N., Suksamrarn A., Chem. Pharm. Bull., 54, 301—305
(2006).
10) Matsumoto K., Akao Y., Yi H., Ohguchi K., Ito T., Tanaka T.,
Kobayashi E., Linuma M., Nozawa Y., Bioorg. Med. Chem., 12,
5799—5806 (2004).
11) Gopalakrishman G., Banumathi B., Suresh G., J. Nat. Prod., 60, 519—
524 (1997).
12) Pham H. H., “The Flora of Vietnam,” Band I, Youth Publisher,
HoChiMinh City, 1999, p. 455.
13) Likhitwitayawuid K., Phadungcharoen T., Krungkrai J., Planta Med.,
64, 70—72 (1998).
14) Na Pattalung P., Thongtheeraparp W., Wiriyachitra P., Taylor W. C.,
Planta Med., 60, 365—368 (1994).
3,6-Di-O-methyl a-Mangostin (16): Yellow fine needles, mp 119—
122 °C; EI-MS C26H30O6, m/z: 437.1 [MꢀH]ꢀ; 1H-NMR (300 MHz, CDCl3)
d: 13.47 (1H, s, 1-OH), 6.71 (1H, s, H-5), 6.29 (1H, s, H-4), 5.23 (2H, t, Jꢁ
6.6 Hz, H-12 and H-17), 4.13 (2H, d, Jꢁ6.6 Hz, H2-16), 3.95, 3.90 and 3.80
(each 3H, s, 3-OMe, 6-OMe and 7-OMe), 3.34 (2H, d, Jꢁ6.6 Hz, H2-11),
1.85, 1.84, 1.80 and 1.68 (each 3H, s, H3-14, H3-15, H3-19 and H3-20); 13C-
NMR (75 MHz, CDCl3) d: 181.2 (C, C-9), 162.1 (C, C-3), 158.6 (C, C-1),
157.0 (C, C-6), 156.6 (C, C-10a), 154.3 (C, C-4a), 142.9 (C, C-7), 137.2 (C,
C-8), 131.4 and 131.2 (C, C-13 and C-18), 123.8 and 122.8 (CH, C-12 and
C-17), 120.5 (C, C-8a), 114.6 (C, C-2), 110.9 (C, C-9a), 97.8 (CH, C-5),
94.2 (CH, C-4), 60.9 (CH3, 7-OMe), 56.0 and 55.8 (CH3, 3-OMe and 6-
OMe), 26.2 (CH2, C-16), 22.4 (CH2, C-11), 25.9 and 25.8 (CH3, C-15 and
C-20), 18.2 and 17.8 (CH3, C-14 and C-19).
15) Ee G. C. L., Izzaddin S. A., Rahmani M., Sukari M. A, Lee. H. L.,
Nat. Prod. Sci., 12, 138—143 (2006).
16) Ee G. C., Cheow Y. L., Asian J. Chem., 20, 343—351 (2008).
17) Sobotta R., Ignatow H. P., Hans P., U.S. Patent 20060014967 (2006).
18) Skehan P., Storeng R., Scudiero D., Monks A., McMahon J., Vistica
D., Warren J. T., Bokesch H., Kenney S., Boyd, M. R., J. Natl. Cancer
Inst., 82, 1107—1112 (1990).
6-O-2-Propenyl a-Mangostin (11): Yellow gum; EI-MS C27H29O6, m/z:
1
449.1 [MꢀH]ꢀ; H-NMR (300 MHz, CDCl3) d: 13.84 (1H, s, 1-OH), 6.74
19) Plumb J. A., Milroy R., Kaye S. B., Cancer Res., 49, 4434—4440
(1989).
(1H, s, H-5), 6.28 (1H, s, H-4), 5.25 (2H, t, Jꢁ7.1 Hz, H-12 and H-17), 5.50
(1H, dd, Jꢁ17.4, 1.3 Hz, HE-23), 5.36 (1H, dd, Jꢁ10.5, 1.3 Hz, HZ-23), 5.10