CYTOTOXICITY EFFECT OF RESVERATROL OLIGOMERS AND THEIR DERIVATIVES AGAINST HUMAN CANCER CELL LINES
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Transcript of CYTOTOXICITY EFFECT OF RESVERATROL OLIGOMERS AND THEIR DERIVATIVES AGAINST HUMAN CANCER CELL LINES
Sri Atuna, Nurfina Aznama, Retno Arianingruma, Takaya Yb, Niwa Masatakeb
a Department Chemistry education, Universitas Negeri Yogyakarta, Karangmalang, Depok, Sleman, Yogyakarta, 55281b Faculty of Pharmacy, Meijo University, Tempaku, Nagoya, Japan
Hopea is one the main genus of Dipterocarpaceae, consisting of approximately 100 species and widely distributed in Indonesia specially in Kalimantan
The local name is “ cengal, merawan hitam or pengarawan”. The plant ussually can be used as material building, plywood etc.
This family of plant is known to produce a variety of resveratrol oligomer
These structures are very interesting and showed interesting biological activity, such as antibacterial, anticancer, antihepatotoxic, and anti-HIV
METHODE OF RESEARCH
Sample: milled dried stem bark
Extraction by organic solvent : acetone or methanol
EXTRACT
By fractionated (VLC)
Fr A Fr B Fr DFr C
Pure compounds S-1, S-2, … etc
Repeated Chromatography
elusidasion structure by Spectroscophy methode(UV, FT-IR, NMR, MS)
BIOACTIVE COMPOUNDS
Methylation & Acethylation
STRUCTURE MOLECULEDERIVATIVES COMPOUNDS
Isolated compounds from H. mengarawan (5 Kg)
O
OH
HH
HOOH
HO
OH
OH
H
H
O
HO
OH
OH
OHHO
OH
HH
H
H
HO
HO
HO
HO
OH
OH
OH
HO
HO
H
H
H HH
H
O
O
HO
HO
HO
HO
HO HO
OHOH
OH
HH
H HHH
H
H
OH
Balanocarpol (300 mg)
Heimiol A (200 mg)
Vaticanol G (70 mg)
vaticanol B (200 mg)
Isolated compounds from H. odorata (3.8 Kg)
O
OH
HH
HOOH
HO
OH
OH
H
H
Balanocarpol (300 mg)
OHO
HO
HO
OH
OH
H
H
H
O
OH
OHHOHO
HO
H
H
H
HH
Hopeaphenol (1500 mg)
O
O
HO
HO
OH
H
H
OH OH
HH
HOHO OH
OH
OH
H
H
H
H
A1
A2
B1
B2
1a
4a
7a
8a
10a12a7b
8b
1b
4b
12b
14b
Ampelopsin H (250 mg)
O
OH
H
HO
OH
HO
OH
OH
H H
H
H H
H
OH
HO
OH
OH
OH
A1
A2
B2
B1
C1
C2
D1
D2
1a
4a
7a
8a
10a12a7b
8b
4b
12b
7c
8c
12c
7d8d
4d
12d
4c
Hemlesyanol C (120 mg)
Isolated compounds from H. nigra (3.5 Kg)
HO
HO
HO
HO
OH
OH
OH
HO
HO
H
H
H HH
H
vaticanol G (200 mg)
Spectrum UV and IR of Vaticanol B
O
O
HO
HO
HO
HO
HO HO
OH OH
OH
H
H
H HHH
H
H
OH
Spectrum 1H and 13C NMR of vaticanol B
O
O
HO
HO
HO
HO
HOHO
OHOH
OH
H
H
H H
H
H
H
H
OH
D1D2
A1
A2
B1
B2
C1
C2
7a
8a
7d
8d
7b
Spectrum 1H-1H COSY NMR of vaticanol B
Methode identification structure by modern spectroscophy
Cytotoxicity test by Hela S3 cell lines
Hela S3 cell lines before experiment Hela S3 cell lines after experiment
Cytotoxicity test by Raji cell lines
Raji cell lines before experiment Raji cell lines after experiment
No Sample LC50 µg/mLHela- S3 Raji Myeloma
123456789101112
Balanocarpol Heimiol AVaticanol G Vaticanol B Hopeaphenol Ampelopsin H Hemlesyanol Deca-methyl-O-hopeaphenol Deca-acethyl-hopeaphenol Penta-methyl-O-balanocarpol Hexa-acethyl-balanocarpol Doxorobicin (positif control)
692.78> 1000> 100092.81
> 1000129.71557.44> 1000> 1000> 1000594,2996,87
235.29> 1000> 100034.45
781.4934.69
292.14> 1000> 1000> 1000594,29242,10
197.61> 1000> 1000
*250,15119.62756.43> 1000> 1000533.85298,06
*
Table 1. The cytotoxic effects of resveratrol oligomers and their derivatives in human cancer cell lines
*Note : not finished yet
Conclusion
In this paper we conclusion that isolated compound from steam bark of H. mengarawan, H.odorata and H. nigra have cytotoxic effect against Raji, HeLa-S3, and Myeloma cell lines. Vaticanol B (4) and ampelopsin H (6) give the highest cytotoxic effect against HeLa-S3 and Raji, while the derivative resveratrol, methyl and acethyl balanocarpol and hopheaphenol showed not active.
Acknowledgements
This work has been supported by competitive grant (Insentif Riset Dasar, Ristek- 2008), Ministry Reseach and Technology, Republic of Indonesia. The authors are grateful to the experimental Garden in Carita, Pandeglang, Banten, Indonesia and Herbarium Bogoriensis for supported the sample and identification of the plant specimen.
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