PHYTOCHEMICAL STUDY OF
OLIGORESVERATROL FROM
SOME SPECIES OF HOPEA
Sri Atun
Department Chemistry education, Universitas Negeri Yogyakarta,
Karangmalang, Depok, Sleman, Yogyakarta, 55281
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
Objective
The following discussion will focus on the
structure diversity of oligoresveratrol that have
been found, biogenetic relationship, and
biological activity of the compound, that has
been reported until 2008
How to isolated oligoresveratrol ?
Sample: milled dried stem bark
Extraction by organic solvent :
acetone or methanol
EKSTRAK
By fractionated (VLC)
Fr. A
Fr. B
Fr. C
Fr. D
Repeated Chromatography
Activity test
BIOACTIVE
COMPOUNDS
Pure compounds
S-1, S-2, … dst
elusidasion structure by
spektroskopi methode
(UV, FT-IR, NMR, MS)
STRUCTURE
MOLECULE
HOW TO ISOLATED COMPOUNDS FROM NATURAL PRODUCT
Maserated by
organic solvent
removal of the
solvent under
reduced
pressure
Prepared for VLC
VLC
Series of fraction
chromatogram from chromatography coloumn
1
4
2
3
5
How to identification these
structure ?
Spektrum UV dan IR Vaticanol B
Spectrum 1H and 13C NMR of vaticanol B
OH
HO HO
HO
HH
OH
H
H
HH
O
HO
OH
HO
H
HO
O
H
OH
Spectrum H-H COSY NMR of vaticanol B
12b
7a
7d
7b
8d 8c
8a
7c
8b
8b
OH
HO
HO
D2
C1
H
HO
7c
D1
H
B1
HO
8d
7b
7d
7a
12b
HO
C2
H
8a
H 7a O
H
A1
O
H
7b
A2
HO
7d
8d
H H
8a
8c
OH
B2
OH
OH
Table 1. Oligoresveratrol compounds from some species of Hopea
Species
Oligoresveratrol
H. odorata (Cogon, 1970),
Hopheaphenol
H. cardifolia (Sotheesswaran,
copaliferol A; stemonoporol
H. jucunda (Diyasena, 1985)
Hopeaphenol
H. malibato (Dai, 1998),
malibatol A; malibatol B ; dibalanokarpol
H. parviflora (Tanaka, 2000),
(-)-ε-viniferin ; (-)-ampelopsin A; balanocarpol; (+)parviflorol ; hopeaphenol
H. utilis (Tanaka, 2001)
vaticanol B; hopeaphenol
H. sangal (Sri Atun, 2004),
(-)-ampelopsin A ; (-)-ε-viniferin ; vaticanol B; hopeaphenol
H. bancana (Tukiran, 2004)
(+)-α-viniferin ; hopeaphenol
H. mengarawan ( Sri Atun,
Balanocarpol; heimiol A; vaticanol G; vaticanol B;
1983)
2006)
H. odorata ( Sri Atun, 20052006)
H. nigra ( Sri Atun, 2006)
balanokarpol; hopeafenol; ampelopsin H; hemlesyanol C
Vaticanol G
Diversity structure oligoresveratrol from Hopea
Monomer and dimer resveratrol
O
HO
H
HO
H
OH
OH
O
H
HO
HO
OH
HO
Resveratrol
(H. utilis)
HO
HH
OH
OH
O
OH
H
OH H
OH
ε-viniferin
(-)-ampelopsin A
(H. parviflora)
(H. parviflora,
OH
(-)-balanokarpol
(H. parviflora)
H. sangal )
HO
HO
OH
HO
O
H H
HO
O
OH
HO
HO
OH
HO
O
OH
OH
OH
OH
H
H
OH
OH
H
H
HO
(+)-parviflorol
(H. parviflora)
HO
OH
Malibatol A
OH
H
OH
HO
H
H
HO
OH
malibatol B
(H. malibato)
Trimer resveratrol
HO
OH
OH
HO
OH
OH
H
HO
H
H
H
HO
OH
H
OH
HO
OH
OH
HO
H
H
H
OH
O
H
H
OH
H
H
OH
OH
O
HO
HH
H
H
O
HO
HO
HO
OH
Stemonoporol
Kopaliferol A
(H. cardifolia)
α-viniferin
(H. cardifolia)
(H. bancana)
OH
Tetramer resveratrol
OH
HO HO
HO
HH
OH
H
HO
OH
H
H
H
HH
HO
O
HO
O
HO
HO
OH
H
OH
HO
HO
Vatikanol B
OH
HO
OH
O
O
H
H
H
OH
OH H
OH
H
HO
OH
OH
(-)-hopeafenol
parviflora, H. utilis, H. bancana
HO
H
H
(H. sangal, H. odorata, H.
(H. sangal, H.
utilis)
HO
H HO
HO
Dibalanokarpol
(H. malibato)
HO
O
H
HO
H
H
H
OH
HO
OH
Tetramer resveratrol
HO
4b
HO
O
B1
H
10a
H
A2
H
A1
7a
1a
H
H
12b
O
H
8b
B2
O
1a
H
OH
7b
H
HO
14b
H
OH
A2
12a
4c
B2
H
OH
C1
OH
H
H
10a
OH
4a
7a
OH
8a
OH
12b
HO
4a
A1
8a
HO
HO
1b
OH
12a
OH
H
7c
8b
8c
12d
H
7b
D2
H
OH
OH
8d
C2
B1
Ampelopsin H (H. odorata)
(Sri Atun, 2005)
4b HO
7d
O
12c
H
D1
OH
4d
OH
Hemlesyanol C (H. odorata)
(Sri Atun, 2006)
OH
HO HO
OH
HO
H
HO
HH
H
HH
H
HO
O
OH
HO
HO
O
HO
H
O
HO
OH
H
HO
O
HO
O
H
HO
OH
OH
HO
OH
OH
HO
OH
OH
HO
O
H
HO
OH
HO
O
OH
HO
OH
HO
HO
HH
OH
OH
HO
O
HO
OH
H H
OH
OH
H H
OH
OH
OH
H
HO
HO
H
H
H
H
H
OH
HO
OH
OH
OH
HO
H
HO
O
H
HH
H
H
OH
OH
HO
H
H
H
H
H
O
H
HO
H H
OH
OH
HO
OH
H
OH
H
HO
HO
HO
O
OH
OH
OH
HO
HO
COOH
NH2
COOH
HO
Biogenetic relationship of oligoresveratrol structure
from Hopea genus
Carbohydrate
Biological activity of oligoresveratrol compounds from
Hopea
H
OH
O
HO
H
HO
OH
HO
O
H
HO
OH
HO
HH
OH
HO
(-)-ampelopsin A
anticancer
antibacterial
sitotoxic
H
OH H
HO
O
O
H
H
H
HO
H
OH
malibatol B
sitotoxic
HO
O
OH
H
HO
OH
OH
OH
HO
H
OH
Malibatol A
HO
H
HO
OH
H H
HO
ε –viniferin
OH
OH
H H
OH
Resveratrol
O
OH
HO
HO
OH
H
HO
OH
O
OH
HO
OH
HO
H
HO
O
OH
OH
HO
OH
OH H
HO
H HO
HO
H
H
H
OH
HO
OH
HO
H
H
HO
OH
(-)balanokarpol
Dibalanokarpol
(-)-hopeafenol
Anti HIV
Anti-HIV
(sitotoxic)
OH
OH
Table 2. Data activity test as hydroxyl radical scavenger
IC50
( g/ml)
Note
Balanocarpol
1802,3
Less active
Heimiol A
4575.3
Less active
Vaticanol G
683.96
active
Vaticanol B
2146.6
Less active
Hopheaphenol
61,8
High active
Ampelopsin H
4840,0
Less active
Hemlesyanol C
425,5
active
Ascorbat acid
83,9
High active
1328,1
Less active
Sample
Butylated Hydroxy Toluene
(BHT)
Table. 4. LC50 of some compounds from steam bark of Hopea
against HeLa-S3 cell
No
Sample
LC50 g/ml
Note
682,16
Less active
1
Balanocarpol
2
Heimiol A
Very high
Not active
3
Vaticanol G
Very high
Not active
4
Ampelopsin H
8,12
Very active
5
Vaticanol B
92,04
Very active
6
Hopeaphenol
1931,52
Less active
7
Hemsleyanol C
531,00
Active
8
Doksorubisin
control)
96,27
Very active
(positif
Table. 5. LC50 of some compounds from steam bark of
Hopea against Raji cell
No
Sample
LC50
g/ml
Note
277,58
Active
1
Balanocarpol
2
Heimiol A
Very high
Not active
3
Vaticanol G
11050,96
Not active
4
Ampelopsin H
91,07
Very active
5
Vaticanol B
107,00
Very active
6
Hopeaphenol
135,64
Active
7
Hemsleyanol C
166,84
Active
8
Doksorubisin (positif control)
156,64
Active
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
FITOFARMAKA ANTIHEPATOTOKSIK EKSTRAK TUMBUHAN H.
MENGARAWAN
Uji aktivitas antihepatotoksik
(Uji Farmakologi)
-Dosis 75 – 300 mg/kg BB
-Dosis 10-50 mg/kg BB
Uji keamanan :
• Toksisitas acut
• Toksisitas subkronis
• Teratogenik
• Mutagenik
Formulasi
Obat herbal
terstandar
(Pendaftaran
Regristasi)
Uji Praklinik Produk Jadi
• Toksisitas acut
• Toksisitas subcronis
Uji Klinik
(Fase 1, 2,3,4)
Standarisasi :
• Bahan baku
• Proses ekstraksi
• Senyawa aktif
(balanokarpol)
Shelf life produk
Analisis proses
produksi;
pemasaran
Conclusion
Molecular structure of oligoresveratrol have ben found in the Hopea
genus included dimer, trimer and tetramer with resveratrol. The structures of
the oligoresveratrol isolated contain a heterocyclic ring namely trans-2-aryl2,3-dihydrobezofuran, originated from oxidative coupling between two unit
of resveratrol to produce (-)-ε-viniferin (2) and other compounds. These
structures are very interesting and showed interesting biological activity,
such as antibacterial, anticancer, antihepatotoxic, and anti-HIV
Acknowledgements
This work was supported by Competitive research (HB 2004-2005); Fundamental
research (2006-2007; Rapid (2007-2009) from Directorate General Higher
Education, Republic of Indonesia; competitive grant (Insentif Riset Dasar, Ristek2008), Ministry Research and Technology, Republic of Indonesia The authors are
grateful to my teamwork Prof. Dr. Nurfina Aznam and Retno Arianingrum, M.Si
(UNY), Prof. Masatake Niwa and Dr. Yoshiaki Takaya (Meijo University, Japan) who
contributed for this study.