全 文 :2016
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Vol41,No.5 March,2016
·
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)(6)、
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(8)、
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(9)、4
Hydroxyphthalid(10)。
Ì$_ñ.
1¯
Ú_ñ.
,
_ñ.
2~10
íQö8µº.$=áÎ
。
ÉÊ
MTT
¶±=_ñ.
1~9
¼n¾23°Â(Ë
,
yóC
,
_ñ.
2
±i¿j
HCT116、
ÙRi¿j
HepG2、
Ùi¿j
BGC823、
Ù:¿j
hi¿j
NCIH1650、
Ùqri¿j
A2780
óCàKôÉÊ
,
mBë&¾23°Â
,
ÌØ_ñ.öÖ¾23ÉÊ]Cà
。
[
qrs
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01
;
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;
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tu)(
] 20151028
[
vwxT
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a7ûü«8ßxy
(cstc2014yykfC10004)
[
yzA{
]
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,Tex/Fax:(023)89029081,Email:yangdaji@hotmailcom;
ea
,Tex/Fax:(023)89029070,Email:cqzhangyi@hot
mailcom
[
A{
]
®¯
,
Îqré
,Email:zengyaobo@126com
ChemicalconstituentsfromMylabrisphalerataand
theircytotoxicactivityinvitro
ZENGYaobo1,LIUXiaoling1,LIChuangjun2,ZHOUXing1,ZHANGXiaomei1,YANGYong1,
DUHongfei1,TANChunbin1,ZHANGYuyu1,ZHANGYi1,YANGDajian1
(1ChongqingAcademyofChineseMaterialMedical,Chongqing400065,China;
2StateKeyLaboratoryofBioactiveSubstanceandFunctionofNaturalMedicine,InstituteofMateriaMedica,
ChineseAcademyofMedicalSciences,PekingUnionMedicalColege,Beijing100050,China)
[Abstact] TencompoundswereisolatedfromMylabrisphaleratabyusingpreparativeHPLCandcolumnchromatographyoverMCI
gelOnthebasisofphysicalchemicalproperties,NMRandMSdataanalysis,thecompoundswereidentifiedas5′[(1R,2R,3S,
6R)1hydroxymethyl2methyl3,6epoxycyclohexane1,2dicarboximide]ethyl2′methyl2′butenoate(1),cantharidin(2),cyclo
(LProLAla)(3),cyclo(RProRLeu)(4),cyclo(SProRLeu)(5),cyclo(DProLTyr)(6),indole3aldehyde(7),3
indoleaceticacid(8),valerolactam(9),and4hydroxyphthalid(10)Compound1wasanewcompound,andcompounds210were
obtainedfromthisgenusforthefirsttimeCompounds19weresubjectedtocytotoxicactivityonHCT116,HepG2,BGC823,NCI
H1650,A2780cellines,andonlycompound2showedinhibitoryefectonalcancercellines
[Keywords] Mylabris;chemicalconstituents;cytotoxicefect
doi:10.4268/cjcmm20160516
·958·
2016
y
3
z ©
41
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5
}
Vol41,No.5 March,2016
01
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sú&Bw0sv
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30%
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5(21mg)
10(9mg);Fr354
(651mg)
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HPLC
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(5mg),4(23mg),7(15mg)。Fr5(18g)
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MCI
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,
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20%,50%,80%,100%
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25%
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8(5mg)。
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1
Cv.
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3381592,[M +H]+ (
Ï ¹
3381598,
C17H24NO6),<¯ C17H23NO6,]þ±¯ 7。
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<
,δH125(3H,s),189(3H,d,J=18Hz),213
(3H,d,J=12Hz);
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H,d,J=116Hz),447(1H,d,J=116Hz);1
ñ
E§< δH562(1H,m)。
13CNMR(CD3OD,150
MHz)
ç$àº
17
ñáv<
,
ñ
DEPT
HSQC
çî2z×_ñ.
1
,B
6
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5
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3
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。
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2
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(δC1806,1832),1ñ|£v< δC
1673,2
ñ]þáv<
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(δC126,207,277)。_ñ.1 NMR
=ª8µ.ö8=áÎ
asymmetriccantha
rimide[7]
,
@Ò<=§ë
,
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,
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1
1HNMR
ç δH189(3H,d,J=18Hz),213(3H,d,J=12
Hz),562(1H,s),360(4H,d,J=24Hz)
ú¥Â
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425,1604,1161,1673
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9,C6′
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q
1,
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1)。
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4
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,
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§Ø[Q
,¯ 1R,2R,3S,6
R
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E}§ØBÞz×
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.
1¯ 5′[(1R,2R,3S,6R)1
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1
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1
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HMBC(H→C)YZv<
Fig1 ThekeyHMBCcorelationofcompound1
ó
1
_ñ.
1
1HNMR
13CNMR
=
Table1 1HNMRand13CNMRspectraldataforcompound1(inCD3OD)
No δH δC No δH δC
1 597 10 420(1H,d,J=116Hz) 611
2 553 447(1H,d,J=116Hz)
3 453(1H,d,J=4Hz) 859 1′ 1673
4 170(1H,m),177(1H,m) 248 2′ 1604
5 171(1H,m),197(1H,m) 256 3′ 562(1H,m) 1161
6 460(1H,d,J=4Hz) 833 4′ 189(3H,d,J=18Hz) 277
7 1806 5′ 360(2H,d,J=16Hz) 425
9 1832 6′ 360(2H,d,J=16Hz) 596
2Me 125(3H,s) 126 2′Me 213(3H,d,J=12Hz) 207
_ñ.
2
>È
(
)z
),[α]25D =+56
(c008,MeOH);ESIMSm/z2192[M+Na]+;
1HNMR(CDCl3,400MHz)δ:124(6H,s,1Me,2
Me),176(2H,m,H4,H5),181(2H,m,H4,H
5),472(2H,brs,H3,H6);13CNMR(CDCl3,125
MHz)δ:127(1Me,2Me),234(C4,C5),552
(C1,C2),847(C3,C6),1759(C7,C9)。
2
¼uç=ª^
[8]
kB=[Q
,
ÝÒ×
µ_ñ.¯01ì
(cantharidin)。
_ñ.
3
·>%¥
(
ëÐ
),[α]25D =-96
(c01,MeOH);ESIMSm/z1912[M +Na]+;
1HNMR(CD3OD,400MHz)δ:139(3H,d,J=72
Hz,9Me),193(1H,m,H4a),200(1H,m,H
4b),202(1H,m,H5a),231(1H,m,H5b),352
(2H,m,H3),425(1H,t,J=84Hz,H6),418
(1H,q,J=64Hz,H9);13CNMR(CD3OD,125
MHz)δ:157(9Me),236(C4),291(C5),464
(C3),521(C9),605(C6),1690(C7),1726
(C1)。
2¼=ª^
[9]
kB=˧P+
±¹[Q
,
ÝÒ×µ_ñ.¯
cyclo(LProLAla)。
_ñ.
4
·>%¥
(
ëÐ
),[α]25D =+138
(c02,MeOH);ESIMSm/z2333[M+Na]+;
1HNMR(CD3OD,400MHz)δ:101(6H,dd,J=
68,52Hz,2Me,13Me),195(1H,m,H4a),
199(1H,m,H4b),204(1H,m,H5a),237(1
H,m,H5b),352(2H,m,H3),386(1H,ddd,
J=92,52,40Hz,H9),428(1H,t,J=80Hz,
H6),159(1H,m,H10a),168(1H,m,H11),
180(1H,m,H10b);13CNMR(CD3OD,125MHz)
δ:205(12Me),216(13Me),219(C4),241(C
11),285(C5),422(C10),455(C3),557(C
9),579(C6),1676(C7),1702(C1)。
^
[10]
kB=˧P+±¹ª2¼=£4[
Q
,
§µ_ñ.
1H,13CNMR
!ñç=
·168·
2016
y
3
z ©
41
ª©
5
}
Vol41,No.5 March,2016
Ò×µ_ñ.¯
cyclo(RProRLeu)。
_ñ.
5
·>%¥
(
)z
),[α]25D =-89
(c008,MeOH);ESIMSm/z2332[M+Na]+;
1HNMR(CDCl3,400MHz)δ:095(3H,d,J=64
Hz,13Me),099(3H,d,J=64Hz,12Me),190
(1H,m,H4a),208(1H,m,H4b),214(1H,m,H
5a),234(1H,m,H5b),353(1H,dt,J=84,36
Hz,H3b),360(1H,dt,J=84,36Hz,H3a),
399(1H,d,J=92,H9),410(1H,t,J=80Hz,
H6),612(1H,s,NH),152(1H,m,H10a),172
(1H,m,H11),193(1H,m,H10b);13CNMR
(CDCl3,125MHz)δ:212(12Me),228(13Me),
233(C4),247(C11),282(C5),386(C10),
455(C3),535(C9),590(C6),1662(C7),
1703(C1)。
2¼=ª^
[10]
kBuç=
˧P+±¹[Q
,
ÝÒ×µ_ñ.¯
cyclo(S
ProRLeu)。
_ñ.
6
Cv.
(
ëÐ
),[α]25D =-51
(c03,MeOH);ESIMSm/z2832[M+Na]+;
1HNMR(CD3OD,400MHz)δ:123(1H,m,H4a),
181(2H,m,H4b,H5a),210(1H,m,H5b),308
(2H,m,H10),359(2H,m,H3),405(1H,m,
H9),437(1H,brs,H6),671(2H,d,J=64Hz,
H3′,H5′),703(2H,d,J=68Hz,H2′,H6′);
13CNMR(125MHz,CD3OD)δ:227(C4),294
(C5),377(C10),459(C3),579(C9),600
(C6),1162(C3′,C5′),1321(C1′),1275
(C2′,C6′),1578(C4′),1670(C7),1708
(C1)。
2¼=ª^
[11]
kBuç=˧P
+±¹[Q
,
ÝÒ×µ_ñ.¯
cyclo(DProLTyr)。
_ñ.
7
·>%¥
(
ëÐ
),ESIMSm/z
1681[M+Na]+;1HNMR(CD3OD,400MHz)δ:
727(2H,m,H6,H7),748(1H,d,J=80Hz,H
8),811(1H,s,H2),818(1H,d,J=76Hz,H
5),990(1H,s,H10);13CNMR(CD3OD,125MHz)
δ:1134(C8),1204(C3),1227(C7),1239
(C6),1253(C5),1260(C4),1392(C9),
1400(C2),1874(C10)。
2¼uç=ª^
[12]
kB=[Q
,
ÝÒ×µ_ñ.¯
indole3
aldehyde。
_ñ.
8
·>%¥
(
ëÐ
),ESIMSm/z
1971[M+Na]+;1HNMR(CD3OD,400MHz)δ:
754(1H,d,J=80Hz,H4),735(1H,d,J=80
Hz,H7),718(1H,s,H2),711(1H,t,J=72Hz,
H6),702(1H,t,J=72Hz,H5),365(2H,s,
H8);13CNMR(CD3OD,125MHz)δ:1193(C2),
1285(C3),1095(C3a),1200(C4),1226
(C5),1249(C6),1123(C7),1381(C7a),
335(C8),1780(C9)。
2¼uç=ª^
[13]
kB=[Q
,
ÝÒ×µ_ñ.¯
3indolea
ceticacid。
_ñ.
9
ñÛ>v.
(
ëÐ
),ESIMSm/z
1222[M+Na]+;1HNMR(CD3OD,400MHz)δ:
179(2H,m,H5),181(2H,m,H4),233(2H,t,
H3),332(2H,m,H6),591(1H,s,NH);
13CNMR(CD3OD,125MHz)δ:1722(C2),424
(C6),315(C3),223(C5),209(C4)。
2¼=
ª^
[14]
kB=[Q
,
ÝÒ×µ_ñ.¯
p8À(
。
_ñ.
10
ñÛ>Èö
(
ëÐ
),HRESIMS
m/z1510388[M+H]+;1HNMR(CD3OD,400
MHz)δ:740(1H,t,J=76Hz,H5),732(1H,d,
J=76Hz,H6),708(1H,d,J=80Hz,H4),
530(2H,s,H3);13CNMR(CD3OD,400MHz)δ:
700(C7),1171(C4),1214(C6),1285(C9),
1320(C5),1351(C8),1542(C3),1741(C
2)。
2¼=ª^
[15]
kBuç=£4[
Q
,
ÝÒ×µ_ñ.¯
4hydroxyphthalid。
4
öÖ¾23°Â(×
4TUÉÊ
MTT
¶±_ñ.
1~9
¼nöÖ¾
23°ÂÅ(
,
-ç±Ùi¿j
HCT116、
ÙR
i¿j
HepG2、
Ùi¿j
BGC823、
Ù:¿jh
i¿j
NCIH1650、
Ùqri¿j
A2780
¼n¿ö
Ö°ÂLM
,
TUyóC
,
_ñ.
2(
01ì
)
ó
CàKôÉÊ
,IC50¯261~387μmol·L
-1,
ÌØ_ñ.
IC50>10μmol·L
-1,
oöÖ±23¿
jKôÉÊ]Cà
。
5
yÀ
4TU801)z1XÖ=áÎ
10
ñ_ñ
.
,
Ì$_ñ.
1¯
Ú_ñ.
,2~10
Qö8µ/º
=áÎ
。
¯¼[ç01_°Â
,
±
_ñ.
1~9
¼nöÖ¾23°ÂLM(×
,
T
UyóC
,
_ñ.
2
±Ùi¿j
HCT116、
Ù
Ri¿j
HepG2、
Ùi¿j
BGC823、
Ù:¿j
·268·
¦Yu
:
01_ËöÖ¾23°Â
hi¿j
NCIH1650、
Ùqri¿j
A2780
íBë
&KôÉÊ
,
¾23ÉÊCà
,
ÌØ_ñ.¾23
°Âëì
。
@ÒöÖ¾23°Â
,
[×Ó±¢
º¿$,01mB¢FW.£»
,
0
1_Ë0°ÂBÞ¤¼[ç
。
[
|}?~
]
[1]
$%,Ò
[1
[S]2015
[2] HuhJE,KangKS,ChaeC,etalRolesofp38andJNKmito
genactivatedproteinkinasepathwaysduringcantharidininduced
apoptosisinU937cels[J].BiochemPharmacol,2004,67:
1811
[3] PengF,WeiYQ,TianL,etalInductionofapoptosisbynor
cantharidininhumancolorectalcarcinomacellines:involvement
oftheCD95receptor/ligand[J].JCancerResClinOncol,
2002,128:223
[4] ChenYN,ChenJC,YinSC,etalEfectormechanismsof
norcantharidininducedmitoticarestandapoptosisinhuman
hepatomacels[J].IntJCancer,2002,100:158
[5] HuanSK,LeeHH,LiuDZ,etalCantharidininducedcyto
toxicityandcyclooxygenase2expressioninhumanbladdercarci
nomacelline[J].Toxicology,2006,223:136
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