Chemical Constituents of Macaranga Andenoceras and Their Cytotoxicity Against P-388 Cells
•
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CHEMICAL CONSTITUENTS OF MACARANGA ANDENOCERAS
AND THEIR CYTOTOXICITY ａｇｉｾｓｔ＠
P-388 CELLS
Auliya Ilmiawati,,·h', Yana M. Syah". Euis H. l-lakim il
"Natural Product Research Group , Organic Chemistry Division,
Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung,
JaJan Ganesha 10, Bandung 40132. Indonesia
hChemistry Department, Bogor Agricultural University
Jalan Agatis Kampus lPB Dramaga, Bogor 16680, Indonesia
*[-mail : ｾ ｬｵｩｾＮＱ＠
ｾ ｜＠
ｾｬｩ＠
Ｎ ｬｩ＠
\'liluu. C(lJl1
Diseminarkan pada acara :
Joint Indonesia-UK conference on Organic and Natural Product Chemistry
Universitas Gadjab Mada,
Yogyakarta-Indonesia, 10-11 Dcsember 2014
(Or. ｔｵｴｊｾ＠
DWl 'W ).
t =
(3)R 1
］Ｇ＼Ｎｾ＠
L
OH
Ｇ｜ｾ＠
0
(4) R = H
(5) R = OH
'
R 2 =H
Fig. I. The constituents isolated from !'vI. udenoceros.
,,
1*
Cytotoxic properties of compounds 1 - 5 were evaluated against murine leukemia P-388
cells according to the method described previously [II], showing their IC so were 10.52, 13.27,
12.99, 33.18, and 67.69, respectively. Compounds 1 -- 3 ex hibited strong cytotoxic properties
while compound 4, the unisoprenylated flavonoL was weakl y active, and compound 5 was
inactive. Thus, C-isoprenylation at the rings A and B of the flavonol greatly enhances its
cytotoxic properties. The presence of a pyran ring in compound 1 could be important for
cytotoxic activity.
Conclusion
Five compounds have bcen isolated from Mocoranga Cll7denoceras, one of them is new
co mpound, namely macaflavonol FOllr known compollnds are glyasperin A, brollssonol E,
Kaempferol , and Quercetin. Macafl avonol, glyasperin A, and brollssonol E exhibited strong
' ytutoxic properties \vhile Macaflavonol have highest activity, with IC so 10,52 pM . Kaempferol
weakly active and Quercetin was not active. PresencL.: of pyran ring in maca flavon ol could be
Important for cytotoxic activity.
-\cknowledgemcn t
Financial support from the Grant of Riset KK - ITB 2013 is gratefully acknowledged. We
1 0 thank the Herbarium of State University of Papua , Indonesia, for identification of the plant
p;:'et men.
Refl:'rences
Blattner F.R., Weising K. , 8anfer G., Mn schwitz U., and Fiala B. (200 I), Molecular
analysis of ph ylogenetic relationships among Myrmecoph ytic Ma caranga species
(Euphorbiaceae). Mol. Phylogen. Evol. 19,331-334.
-=1 Yoder B.J., Cao S., Norris A., Miller J.S. , Ratovoson F., Ra zafitsalama J.,
Andriantsiferana R., Rasamison V.E., and Kingston DGI. (2007 V Antiproliferative
prcnylated stilbcnes and l1avol1oids from Mo carang a a/ni/()/ia from the Madagascar
Rainforest. J. Nat. Prod. 70,3 42-346.
·2 J K3\Nakalli S., Harinantenaina L., Matsunami K. , Otsuka [I., Shinzato T., and Takeda Y.
(2008),
acatlavanones A-G, prenylated tlavanollcs from thc leaves of Macarango
{([norius. J. Nat. Prod. 71,1872-1876.
_ 1 Syah Y.M. , Hakim E.H., Achrnad S.A., Hanafi M., and Ghi sa lberti E.L. (2009 1-"
fsoprenylated flavanones and dihydrochalcones from iViac([J"((nga lrichocarp([. Nat.
Prod. Commun. 4, 63-67 .
. . ] Tanjung M., Hakim E.H.., Mllja hidin D. , [-Iana fi M., and Sya h Y.M . (2009)1
Macagigantin, a farnesyl ated flavonol from Ma caranga g igo l7l ea . 1. Asian Nat. Prod.
Res. 11 ,929-932 .
r -J Tanjung M., Mujahidin D., I-Iakim E.B., Darmawan A., and Syab Y.M. (20 I0)
Geranylated tlavonols from Ma c(f mnga rhizinoides . Nat. Prod. COI11mun. 5, 1209-1211.
Tanjung M., Hakim E.H., Elfahmi , Latip ./., and Syah, Y.M. (2012) , Dihydroflavonol
and flavonol deriv atives from Macaranga reel/no/a. Nat. Prod. Co mmun . 7, [3091310.
rJ
• i
,
Agustina W., JuYiawaty L.D., Hakim E.H., and Syah Y.M. (2012), Flavonoids from
Mocaranga Im,vii, ITB J. Sci. 44A , 1318,
[9 J Syah Y,M, and Ghisalberti E.L (20 I 0), I.f>henolic derivatives with an irregular
sesqlliterpenyl side chain from Mocaronga pruil1osa. Nat. Prod, Commun. 5,219222,
[ 10] Syah Y,M. ancl Ghisalberti E.L. (2012), More phenolic derivatives with an irregular
sesquiterpenyl side chain from Mucaral1ga prllil1os({, Nat. Prod. J 2, 4549,
( II] Sahiclin, Hakim E.H., JlIliawaty L.D. , Syah Y,M ., Din L.B" Ghisalberti E,L., Latip L
Said I.M., and Achmad S,A, (2005),\"Cytotoxic properties of oligostilbenoids from the
tree bark of Hop ea d,yobalanoides, Z, Naturforsch. 60c, 723727,
12] Son K,H" Keon SJ" Chang H,W., Kim RP., Kang S,S . (2001), Papyri flavonol A, a
new prenylated flavonol from Broussonetia popvrilera, Fitoterapia 72,456458,
. 13 J Zeng L, Fukai T., Nomura T., Zhang R, Y " Lou Z,c. (19()2), Phenolic constituents of
Glycyrrhiza species. 8, four new prcnylatcd tlavonoids, glyasperins A. B, C, and D
from the roots of Glyc.:vrrhizo ospem. Heterocycles 34, 575587,
I+J Ternai B. and Markham K,R, (1976), Carbon13 NMR Studies of flavonoidsl.
Flavones and flavonol s. Tetrahedron 32,565569 .
.] Le Bon AM, Siess MH, Organosulfur compounds from allium and the chemoprevention
of cancer. Drug Metabol Drug Interact 2000, 17,51 79.
l8]
f
CHEMICAL CONSTITUENTS OF MACARANGA ANDENOCERAS
AND THEIR CYTOTOXICITY ａｇｉｾｓｔ＠
P-388 CELLS
Auliya Ilmiawati,,·h', Yana M. Syah". Euis H. l-lakim il
"Natural Product Research Group , Organic Chemistry Division,
Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung,
JaJan Ganesha 10, Bandung 40132. Indonesia
hChemistry Department, Bogor Agricultural University
Jalan Agatis Kampus lPB Dramaga, Bogor 16680, Indonesia
*[-mail : ｾ ｬｵｩｾＮＱ＠
ｾ ｜＠
ｾｬｩ＠
Ｎ ｬｩ＠
\'liluu. C(lJl1
Diseminarkan pada acara :
Joint Indonesia-UK conference on Organic and Natural Product Chemistry
Universitas Gadjab Mada,
Yogyakarta-Indonesia, 10-11 Dcsember 2014
(Or. ｔｵｴｊｾ＠
DWl 'W ).
t =
(3)R 1
］Ｇ＼Ｎｾ＠
L
OH
Ｇ｜ｾ＠
0
(4) R = H
(5) R = OH
'
R 2 =H
Fig. I. The constituents isolated from !'vI. udenoceros.
,,
1*
Cytotoxic properties of compounds 1 - 5 were evaluated against murine leukemia P-388
cells according to the method described previously [II], showing their IC so were 10.52, 13.27,
12.99, 33.18, and 67.69, respectively. Compounds 1 -- 3 ex hibited strong cytotoxic properties
while compound 4, the unisoprenylated flavonoL was weakl y active, and compound 5 was
inactive. Thus, C-isoprenylation at the rings A and B of the flavonol greatly enhances its
cytotoxic properties. The presence of a pyran ring in compound 1 could be important for
cytotoxic activity.
Conclusion
Five compounds have bcen isolated from Mocoranga Cll7denoceras, one of them is new
co mpound, namely macaflavonol FOllr known compollnds are glyasperin A, brollssonol E,
Kaempferol , and Quercetin. Macafl avonol, glyasperin A, and brollssonol E exhibited strong
' ytutoxic properties \vhile Macaflavonol have highest activity, with IC so 10,52 pM . Kaempferol
weakly active and Quercetin was not active. PresencL.: of pyran ring in maca flavon ol could be
Important for cytotoxic activity.
-\cknowledgemcn t
Financial support from the Grant of Riset KK - ITB 2013 is gratefully acknowledged. We
1 0 thank the Herbarium of State University of Papua , Indonesia, for identification of the plant
p;:'et men.
Refl:'rences
Blattner F.R., Weising K. , 8anfer G., Mn schwitz U., and Fiala B. (200 I), Molecular
analysis of ph ylogenetic relationships among Myrmecoph ytic Ma caranga species
(Euphorbiaceae). Mol. Phylogen. Evol. 19,331-334.
-=1 Yoder B.J., Cao S., Norris A., Miller J.S. , Ratovoson F., Ra zafitsalama J.,
Andriantsiferana R., Rasamison V.E., and Kingston DGI. (2007 V Antiproliferative
prcnylated stilbcnes and l1avol1oids from Mo carang a a/ni/()/ia from the Madagascar
Rainforest. J. Nat. Prod. 70,3 42-346.
·2 J K3\Nakalli S., Harinantenaina L., Matsunami K. , Otsuka [I., Shinzato T., and Takeda Y.
(2008),
acatlavanones A-G, prenylated tlavanollcs from thc leaves of Macarango
{([norius. J. Nat. Prod. 71,1872-1876.
_ 1 Syah Y.M. , Hakim E.H., Achrnad S.A., Hanafi M., and Ghi sa lberti E.L. (2009 1-"
fsoprenylated flavanones and dihydrochalcones from iViac([J"((nga lrichocarp([. Nat.
Prod. Commun. 4, 63-67 .
. . ] Tanjung M., Hakim E.H.., Mllja hidin D. , [-Iana fi M., and Sya h Y.M . (2009)1
Macagigantin, a farnesyl ated flavonol from Ma caranga g igo l7l ea . 1. Asian Nat. Prod.
Res. 11 ,929-932 .
r -J Tanjung M., Mujahidin D., I-Iakim E.B., Darmawan A., and Syab Y.M. (20 I0)
Geranylated tlavonols from Ma c(f mnga rhizinoides . Nat. Prod. COI11mun. 5, 1209-1211.
Tanjung M., Hakim E.H., Elfahmi , Latip ./., and Syah, Y.M. (2012) , Dihydroflavonol
and flavonol deriv atives from Macaranga reel/no/a. Nat. Prod. Co mmun . 7, [3091310.
rJ
• i
,
Agustina W., JuYiawaty L.D., Hakim E.H., and Syah Y.M. (2012), Flavonoids from
Mocaranga Im,vii, ITB J. Sci. 44A , 1318,
[9 J Syah Y,M, and Ghisalberti E.L (20 I 0), I.f>henolic derivatives with an irregular
sesqlliterpenyl side chain from Mocaronga pruil1osa. Nat. Prod, Commun. 5,219222,
[ 10] Syah Y,M. ancl Ghisalberti E.L. (2012), More phenolic derivatives with an irregular
sesquiterpenyl side chain from Mucaral1ga prllil1os({, Nat. Prod. J 2, 4549,
( II] Sahiclin, Hakim E.H., JlIliawaty L.D. , Syah Y,M ., Din L.B" Ghisalberti E,L., Latip L
Said I.M., and Achmad S,A, (2005),\"Cytotoxic properties of oligostilbenoids from the
tree bark of Hop ea d,yobalanoides, Z, Naturforsch. 60c, 723727,
12] Son K,H" Keon SJ" Chang H,W., Kim RP., Kang S,S . (2001), Papyri flavonol A, a
new prenylated flavonol from Broussonetia popvrilera, Fitoterapia 72,456458,
. 13 J Zeng L, Fukai T., Nomura T., Zhang R, Y " Lou Z,c. (19()2), Phenolic constituents of
Glycyrrhiza species. 8, four new prcnylatcd tlavonoids, glyasperins A. B, C, and D
from the roots of Glyc.:vrrhizo ospem. Heterocycles 34, 575587,
I+J Ternai B. and Markham K,R, (1976), Carbon13 NMR Studies of flavonoidsl.
Flavones and flavonol s. Tetrahedron 32,565569 .
.] Le Bon AM, Siess MH, Organosulfur compounds from allium and the chemoprevention
of cancer. Drug Metabol Drug Interact 2000, 17,51 79.
l8]