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Hidayat, Farabi, Harneti, Maharani, Darwati, Mayanti, Setiawan, Supratman, and Shiono: Cytotoxicity and Structure Activity Relationship of Dammarane-Type Triterpenoids from the Bark of Aglaia elliptica against P-388 Murine Leukemia Cells
Original Article

Natural Product Sciences 2017;23(4):291-298.

Published online: 20 January 2017

DOI: https://doi.org/10.20307/nps.2017.23.4.291

Cytotoxicity and Structure Activity Relationship of Dammarane-Type Triterpenoids from the Bark of Aglaia elliptica against P-388 Murine Leukemia Cells

Ace Tatang Hidayat1, 2, Kindi Farabi1, Desi Harneti1, Rani Maharani1, 2, Nurlelasari Darwati1, Tri Mayanti1, Arlette Suzy Setiawan3, Unang Supratman1, 2, ∗, Yoshihito Shiono4

1Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor 45363, Indonesia

2Central Laboratory of Universitas Padjadjaran, Jatinangor 45363, Indonesia

3Department of Pediatric Dentistry, Faculty of Dentistry, Universitas Padjadjaran, Jatinangor 45363, Indonesia.

4Department of Food, Life, and Environmental Science, Faculty of Agriculture, Yamagata University, Tsuruoka, Yamagata 997–8555, Japan

∗Author for correspondence Unang Supratman, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jatinangor 45363, Indonesia Tel: +62-22-7794391; E-mail: unang.supratman@unpad.ac.id

Received 15 September 2017       Revised 2 October 2017       Accepted 3 October 2017

Copyright © 2017 The Korean Society of Pharmacognosy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Six dammarane-type triterpenoids, dammar-24-en-3β-ol (1), 3β-epicabraleahydroxy lactone (2), (E)-25-hydroperoxydammar-23-en-3β,20-diol (3), dammar-24-en-3β,20-diol (4), 3β-acetyl-20S, 24S-epoxy-25-hydroxy-dammarane (5), and 3β-epiocotillol (6) were isolated from the methanolic extract of the bark of Aglaia elliptica. The chemical structure were identified on the basis of spectroscopic evidence and by comparison with those spectra previously reported. Compounds 1 – 6 were isolated first time from this plant. Compounds 1 – 6, along with a known synthetic analog, cabraleone (7) were evaluated their cytotoxic activity against P-388 murine leukimia cells in vitro. Among those compounds 3β-acetyl-20S, 24S-epoxy-25-hydroxydammarane (5) showed strongest cytotoxic activity with IC50 value of 8.02 ± 0.06 μM.

Keywords: Dammarane-type Triterpenoids, Aglaia elliptica, Meliaceae, P-388 murine leukimia cell

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Fig. 1.
The structures of 1 – 7 isolated from A. elliptica.
nps-23-291f1.tif
Fig. 2.
Key HMBC (→) and COSY (−) correlations of 1 – 6.
nps-23-291f2.tif
Table 1.
13C-NMR data for compounds 1 – 7 (150 MHz in CDCl3)
No. 1 δc (mult.) 2 δc (mult.) 3 δc (mult.) 4 δc (mult.) 5 δc (mult.) 6 δc (mult.) 7 δc (mult.)
1 33.7 (t) 35.2 (t) 39.1 (t) 33.7 (t) 34.3 (t) 33.7 (t) 34.3 (t)
2 24.6 (t) 33.7 (t) 24.9 (t) 24.9 (t) 24.8 (t) 25.4 (t) 26.0 (t)
3 75.0 (d) 76.3 (d) 79.1 (d) 76.4 (d) 78.5 (d) 76.4 (d) 218.3 (s)
4 37.5 (s) 37.3 (s) 39.0 (s) 37.7 (s) 36.8 (s) 37.3 (s) 37.1 (s)
5 49.2 (d) 49.4 (d) 55.9 (d) 49.6 (d) 50.6 (d) 49.6 (d) 49.9 (d)
6 18.1 (t) 18.3 (t) 18.3 (t) 18.3 (t) 18.2 (t) 18.3 (t) 19.8 (t)
7 35.2 (t) 26.9 (t) 35.3 (t) 35.2 (t) 35.3 (t) 34.8 (t) 34.8 (t)
8 40.6 (s) 40.6 (s) 40.4 (s) 40.7 (s) 40.6 (s) 40.7 (s) 40.5 (s)
9 49.5 (d) 50.4 (d) 50.7 (d) 50.4 (d) 50.8 (d) 50.7 (d) 50.4 (d)
10 37.2 (d) 37.7 (s) 37.2 (s) 37.3 (s) 37.2 (s) 37.7 (s) 37.2 (s)
11 21.3 (t) 25.4 (t) 21.6 (t) 21.4 (t) 21.7 (t) 21.7 (t) 21.2 (t)
12 25.7 (t) 21.3 (t) 27.5 (t) 25.4 (t) 27.1 (t) 27.1 (t) 27.4 (t)
13 42.0 (d) 43.2 (d) 42.5 (d) 42.3 (d) 42.8 (d) 42.8 (d) 43.2 (d)
14 50.3 (s) 50.3 (s) 50.4 (s) 50.5 (s) 50.2 (s) 50.2 (s) 50.2 (s)
15 31.1 (t) 31.2 (t) 31.2 (t) 31.2 (t) 31.6 (t) 31.5 (t) 31.6 (t)
16 27.7 (t) 25.1 (t) 27.6 (t) 27.6 (t) 25.9 (t) 25.9 (t) 26.6 (t)
17 50.6 (d) 49.5 (d) 50.3 (d) 49.8 (d) 49.9 (d) 49.8 (d) 55.5 (d)
18 15.8 (q) 15.6 (q) 15.6 (q) 15.6 (q) 15.6 (q) 16.2 (q) 16.2 (q)
19 15.1 (q) 16.1 (q) 16.5 (q) 16.1 (q) 16.1 (q) 16.6 (q) 16.5 (q)
20 38.7 (d) 90.3 (s) 75.2 (s) 75.5 (s) 86.7 (s) 86.7 (s) 86.7 (s)
21 25.1 (q) 25.4 (q) 25.8 (q) 25.5 (q) 27.4 (q) 27.3 (q) 27.2 (q)
22 41.2 (t) 31.3 (t) 43.4 (t) 40.6 (t) 35.2 (t) 35.3 (t) 34.9 (t)
23 22.5 (t) 29.3 (t) 127.4 (d) 22.6 (t) 26.4 (t) 26.4 (t) 26.9 (t)
24 125.3 (d) 176.9 (s) 137.4 (d) 124.8 (d) 86.4 (d) 86.3 (d) 86.5 (d)
25 130.5 (s)   82.2 (s) 131.7 (s) 70.4 (s) 70.3 (s) 70.4 (s)
26 25.2 (q)   24.2 (q) 25.9 (q) 28.0 (q) 27.9 (q) 28.0 (q)
27 16.9 (q)   24.5 (q) 17.8 (q) 24.1 (q) 24.1 (q) 24.2 (q)
28 28.3 (q) 28.4 (q) 28.1 (q) 28.4 (q) 27.9 (q) 28.4 (q) 22.5 (q)
29 21.8 (q) 22.2 (q) 15.4 (q) 22.2 (q) 21.8 (q) 22.2 (q) 22.3 (q)
30 16.2 (q) 16.4 (q) 16.3 (q) 16.6 (q) 16.7 (q) 15.6 (q) 15.4 (q)
1'         171.1 (s)    
2'         21.5 (q)    
Table 2.
Cytotoxicity activity of compounds 1 – 7 against P-388 murine leukemia cells
Compounds IC50 (µM)
Dammar-24-en-3α-ol (1) 21.30 ± 0.06
3-epicabraleahydroxy lactone (2) 104.71 ± 0.05
(E)-25-hydroperoxydammar-23-en-3β,20-diol (3) 12.41 ± 0.04
Dammar-24-en-3β,20-diol (4) 50.44 ± 0.04
3α-acetyl-20S, 24S-epoxy-25-hydroxydammarane (5) 8.20 ± 0.06
3-epiocotillol (6) 23.94 ± 0.04
Cabraleone (7) 32.86 ± 0.04
Artonin E∗ 0.68 ± 0.05

∗ Positive control

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