Cytotoxic biotransformed products from andrographolide by Rhizopus stolonifer ATCC 12939

被引：19

作者：

He, Xiangjiu ^{[1
]}

Zeng, Xiaobin ^{[1
]}

Hu, Hui ^{[1
]}

Wu, Yixuan ^{[1
]}

机构：

[1] Wuhan Univ, Coll Pharm, Wuhan 430072, Peoples R China

来源：

JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC | 2010年 / 62卷 / 3-4期

关键词：

Andrographolide; Microbial transformation; Rhizopus stolonifer; Oxidative products; Antiproliferative activities; CELL-CYCLE ARREST; HUMAN URINE; KAPPA-B; PANICULATA; METABOLITES; ACTIVATION; APOPTOSIS; RATS; IDENTIFICATION; DITERPENOIDS;

D O I：

10.1016/j.molcatb.2009.11.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Biotransformation of andrographolide (1) by Rhizopus stolonifer ATCC 12939 was investigated. Ten bioconversion products were isolated and identified. Their structures were elucidated by high resolution mass spectroscopy (HR-MS), extensive NMR techniques, including (1)H NMR, (13)C NMR, DEFT, (1)H-(1)H correlation spectroscopy (COSY), two dimensional nuclear Overhauser effect correlation spectroscopy (NOESY), heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond coherence (HMBC). Their structures were identified to be 12(R),13(R)-12-hydroxyandrographolide (2), 12(S),13(S)-12-hydroxyandrographolide (3), isoandrographolide (4), 3-dehydro-isoandrographolide (5), 14-deoxy-11,12-didehydroandrographolide (6), 3-oxo-14-deoxy-11,12-didehydroandrographolide (7), 3-dehydroandrographolide (8),14-deoxyandrographolide (9), 3-dehydro-14-deoxyandrographolide (10) and 3-dehydro-14-deoxyandrographolide-19-oic acid (11). Among them, compounds 5 and 11 are novel compounds. The biosynthetic pathways of andrographolide by R. stolonifer were proposed. Most of the products showed potential antiproliferative activities against human breast cancer (MCF-7), human colon cancer (HCT-116) and human leukemia (HL-60) cell lines, and their structure-activity relationships (SAR) were discussed in detail. (C) 2009 Elsevier B.V. All rights reserved.

引用

页码：242 / 247

页数：6

共 27 条

[1] Andrographolide inhibits IFN-γ and IL-2 cytokine production and protects against cell apoptosis [J].

Burgos, RA ;

Seguel, K ;

Perez, M ;

Meneses, A ;

Ortega, M ;

Guarda, MI ;

Loaiza, A ;

Hancke, JL .

PLANTA MEDICA, 2005, 71 (05) :429-434

[2]

Calabrese C, 2000, PHYTOTHER RES, V14, P333, DOI 10.1002/1099-1573(200008)14:5<333::AID-PTR584>3.0.CO

[3]

2-D

[4] Andrographolide reduces IL-2 production in T-cells by interfering with NFAT and MAPK activation [J].

Carretta, Maria D. ;

Alarcon, Pablo ;

Jara, Evelyn ;

Solis, Loreto ;

Hancke, Juan L. ;

Concha, Ilona I. ;

Hidalgo, Maria A. ;

Burgos, Rafael A. .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2009, 602 (2-3) :413-421

[5] Nine new ent-labdane diterpenoids from the aerial parts of Andrographis paniculata [J].

Chen, Li-Xia ;

Qiu, Feng ;

Wei, Hong ;

Qu, Ge-Xia ;

Yao, Xin-Sheng .

HELVETICA CHIMICA ACTA, 2006, 89 (11) :2654-2664

[6] ent-labdane diterpenoid lactone stereoisomers from Andrographis paniculata [J].

Chen, Lixia ;

Zhu, Huajie ;

Wang, Rui ;

Zhou, Kailan ;

Jing, Yongkui ;

Qiu, Feng .

JOURNAL OF NATURAL PRODUCTS, 2008, 71 (05) :852-855

[7] Andrographolide isolated from Andrographis paniculata induces cell cycle arrest and mitochondrial-mediated apoptosis in human leukemic HL-60 cells [J].

Cheung, HY ;

Cheung, SH ;

Li, JL ;

Cheung, CS ;

Lai, WP ;

Fong, WF ;

Leung, FM .

PLANTA MEDICA, 2005, 71 (12) :1106-1111

[8] Isolation and identification of seven glucuronide conjugates of andrographolide in human urine [J].

Cui, L ;

Qiu, F ;

Yao, XS .

DRUG METABOLISM AND DISPOSITION, 2005, 33 (04) :555-562

[9] Four new andrographolide metabolites in human urine [J].

Cui, L ;

Qiu, F ;

Wang, NL ;

Yao, XS .

CHEMICAL & PHARMACEUTICAL BULLETIN, 2004, 52 (06) :772-775

[10]

Cui Liang, 2008, Drug Metab Lett, V2, P261, DOI 10.2174/187231208786734148

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