Two chalcone derivatives, 2-hydroxychalcone (1) n desmethyl infectocaryone (2), together

with five known phenolic compounds infectocaryone (3), cryptocaryone (4), kurzichalcolactone A
(5), pinocembrin (6) and trans-N-feruloyl tyramine (7), were isolated from the methanol extract
of the wood of Cryptocarya konishii. The structures of the new compounds were determined
based on the analysis of spectroscopic data, including UV, IR, 1D and 2D NMR, and mass
spectra. Evaluation of the cytotoxic and tyrosine kinase inhibitory activities of compounds 17
showed that compounds 24 strongly inhibited the growth of murine leukemia P-388 cells,
whereas compound 4 significantly inhibited the enzyme.
Introduction
The genus cryptocarya (lauraceae) contains at least 200 species distributed mainly
in the tropical region of the world. Phytochemical studies have revealed that this
genus produces alkaloids , 2-pyrones and flavonoids as the main secondary
metabolite constituents, e.g. see [2-10]. Recently , we reported chalcone and
flavanone derivatives from C,costata that exhibited cytotoxic activity against
murine leukemia P-388 cells [9]. In continuation of our work on phytochemistry and
biological evaluation of the metabolites from lauraceous plants, we examined the
activity of the MeOH extract of the tree bark of C. konishii Hayata grown in
Indonesia against P-388 cells and tyrosine kinase, showing it significantly inhibited
both the cells (IC50 6.5 ug/mL) and the enzyme (% inhibition of 48.9 at 100 ug/mL).
this plant has been shown to contain a number of alkaloid derivatives [11-13]. In
this paper, we report the isolation of two new chalcone derivatives, 2hydroxychalcone (1) and desmethylinfectocaryone (2), along with the wood of the
title plant, as well as their cytotoxic and inhibitory properties against P-388 cells and
tyrosine kinase.
Result and discussion
Compound 1, isolated as a yellowish powder, exhibited a molecular ion at m/z
224,0840 in the high resolution electron ionization mass spectrum, corresponding to
a molecular formula. C15h12o2 (called 224.0837). the UV spectrum of 1 showed
maxima that were comparable with a chaconne chromophore, and the IR spectrum
exhibited absorptions for hydroxyl, aromatic or akenyl, conjugated carbonyl and
aromatic groups. In the 13C NMR spectru (APT, attached proton test) (tabel1), 1
showed 13 carbon signals representing 15 carbon atoms, all of them havig chemical
shift of sp2 carbon, in which two of the signals were assignable to a conjugated
carbonyl and oxyaryl carbon atom. These spectroscopic data suggested that 1 is a
simple monohydroxylated chalcone derivative. The H NMR spectrum of 1 showed a
characteristic signal of a chalcone structure by the presence of a pair of doublets at
and with a trans coupling constant. The phenolic OH group was determinate to
be at C-2 by the observation in the H NMR spectrum of a chelated OH signal at
and four aromatic signals () with multiplicities typical for a 1,2-disubstituted
benzene. Consequently, the ring B in 1 was an unsubstituted phenyl group ( and
) compound 1, therefore, was assigned as 2-hydroxychalcone. Futher support for

the structure 1 was obtained from the one and two/three-bond H-13C correlations
found in the heteronuclear multiple quantum coherence and heteronuclear multiple
bond connectivity apectra of 1 as shown in table 1. A literature search disclosed
that this compound has been synthesized by guidugli et al. in order to study its
mass spectroscopic behavior, but this paper is the first report of its occurrence from
natural sources.

Compound 2, isolated as a brownish solid , had a molecular formula C17H16O4

based on its high resolution EIMS which showed a molecular ion at m/z 284.1045
(calde 284.1049). the IR spectrum of 2 exhibited absorptions for hydroxyl (), alkyl
(), carboxylic and conjugated carbonyl ( and) and aromatic groups. The UV
spectrum (. Nm) was very close to those of infectocaryone (3) and cryptocaryone
(4), which werw also isolated from the title plant. Comparison of the H and 13C MNR
spectra pf the compound 2 and 3 also resealed a structural similiarity of these two
compound. The most significant differences observed are the appearance of a
proton signal of a methoxyl ester group in 3, which is absent in compound 2, as well
as the presence of the carbon signal characteristic for a carboxylic group at in 2,
instead of a signal of for the aster carbon of 3. In addition, the low resolution (LR)
EIMS of compound 2 gave the same base peak at m/z 131 and a strong peak at m/z
225. The latter peak is very indicative for the presence of carboxylic group in 2,
which can be rationalized as a loss of a CH2Cooh radical from the molecular ion.
Moreover , the presence of a peak at m/z 266, due to a loss of water molecular from
the molecular ion, gave further support for the presence of this group in 2. Thus,
structure 2 was assigned as desmethylinfectocaryone. The one- and two/three-bond
1H-13C correlations observed in the HMQC and HMBC spectra of compound 2 (table
2) were consistent with the structure of desmethylinfectocaryone. By comparison of
the optical rotation values, compound 2 was assumed to have the same
stereochemistry as those of compound 3. Compounds 2-4 represent the members of
naturally occurring chalcone containing a reduced a ring at C-5 and C-6. Compound
3 had previously been isolated from C. infectoria, whereas compound 4 was initially
isolated in 1973 C. bourdilloni.
The isolated compound 1-7 were evaluated for their cytotoxicities against P388 cells and their inhibitory properties against tyrosine kinase (table 3). From the
bioactivity data shown in the table, compound 2-4 showed strong cytotoxic
properties, whereas compound 4 was the only compound with significant inhibitory
effect against tyrosine kinase. Thus, compounds 2-4 could be promising lead
compounds for cancer treatment.

Experimental
General

UV and IR spectra were measured with varian 100 conc and FTIR spectrum one
perkin-elmer instruments, respectively.
Artinya:
Senyawa fenolik dari Cryptocarya konishii: sitotoksik dan tyrosine kinase sifat
penghambatan mereka
Dua derivatif chalcone, 2'-hydroxychalcone (1) dandesmethylinfectocaryone (2), bersama-sama
dengan
limasenyawa fenolik dikenal infectocaryone (3), cryptocaryone (4),kurzichalcolactone A (5), pino
cembrin (6) dan trans-N-feruloyltyramine (7), diisolasi dari ekstrak
metanol kayuCryptocarya konishii. Struktur senyawa baru ditentukanberdasarkan
analisis data spektroskopi, termasuk UV, IR, 1Ddan 2D NMR, dan spektrum
massa. Evaluasi sitotoksik dantirosin kinase kegiatan penghambatan senyawa 1-7menunjukkan
bahwa senyawa 2-4 sangat menghambat pertumbuhan murine leukemia P388 sel, sedangkan senyawa 4secara signifikan menghambat enzim
pengantar
Genus Cryptocarya (Lauraceae) mengandung setidaknya 200 spesies didistribusikan terutama
di daerah tropis di dunia. Studi fitokimia telah mengungkapkan bahwa genus ini menghasilkan
alkaloid, 2-pyrones dan flavonoid sebagai konstituen metabolit sekunder utama, misalnya lihat
[2-10]. Baru-baru ini, kami melaporkan chalcone dan flavanon turunan dari C, costata yang
menunjukkan aktivitas sitotoksik terhadap murine leukemia P-388 sel [9]. Dalam kelanjutan dari
pekerjaan kami pada fitokimia dan evaluasi biologis metabolit dari tanaman lauraceous, kami
menguji aktivitas ekstrak MeOH dari kulit batang C. konishii Hayata tumbuh di Indonesia
terhadap P-388 sel dan tirosin kinase, menunjukkan secara signifikan menghambat kedua sel
(IC50 6,5 ug / mL) dan enzim (% penghambatan 48,9 pada 100 ug / mL). tanaman ini telah
terbukti mengandung sejumlah derivatif alkaloid [11-13]. Dalam tulisan ini, kami melaporkan
isolasi dua turunan chalcone baru, 2'-hydroxychalcone (1) dan desmethylinfectocaryone (2),
bersama dengan kayu dari tanaman judul, serta sitotoksik dan sifat penghambatan terhadap P388 sel dan tirosin kinase.
Hasil dan diskusi
Senyawa 1, terisolasi sebagai bubuk kekuningan, dipamerkan ion molekul
pada m / z 224,0840 dalam resolusi tinggi spektrum massa ionisasi
elektron, sesuai dengan rumus molekul. C15h12o2 (disebut 224,0837).
spektrum UV dari 1 menunjukkan maxima yang sebanding dengan
kromofor Chaconne, dan spektrum IR menunjukkan serapan untuk
hidroksil, aromatik atau akenyl, terkonjugasi karbonil dan kelompok
aromatik. Dalam spectru 13C NMR (APT, uji terpasang proton) (tabel1), 1
menunjukkan 13 sinyal karbon yang mewakili 15 atom karbon, semuanya
pergeseran kimia havig dari sp2 karbon, di mana dua dari sinyal yang
dialihkan ke karbonil terkonjugasi dan oxyaryl atom karbon. Maskapai

data spektroskopi menunjukkan bahwa 1 adalah monohydroxylated

chalcone derivatif sederhana. The H NMR dari 1 menunjukkan sinyal
karakteristik struktur chalcone dengan kehadiran sepasang doublet di ...
dan ... dengan kopling konstan trans. The fenolik -OH kelompok itu tentu
berada di C-2 oleh pengamatan di H NMR spektrum sinyal -OH chelated
di ... dan empat sinyal aromatik (...) dengan multiplicities khas untuk
benzena 1,2-disubstitusi. Akibatnya, cincin B pada 1 adalah kelompok
tersubstitusi fenil (... dan ...) senyawa 1, oleh karena itu, ditugaskan
sebagai 2'-hydroxychalcone. Dukungan LEBIH untuk struktur 1 diperoleh
dari satu - dan dua / korelasi H-13C tiga ikatan 'yang ditemukan di
heteronuklir ganda koherensi kuantum dan heteronuklir beberapa
konektivitas obligasi apectra dari 1 seperti yang ditunjukkan dalam tabel
1. Sebuah pencarian literatur mengungkapkan bahwa ini senyawa telah
disintesis oleh guidugli et al. dalam rangka untuk mempelajari perilaku
spektroskopi massa, tapi kertas ini adalah laporan pertama dari kejadian
tersebut dari sumber alami.