In vitro cytotoxicity of melleolide antibiotics: Structural and mechanistic aspects

被引：41

作者：

Bohnert, Markus ^{[1
]}

Miethbauer, Sebastian ^{[1
]}

Dahse, Hans-Martin ^{[2
]}

Ziemen, Johannes ^{[1
]}

Nett, Markus ^{[2
]}

Hoffmeister, Dirk ^{[1
]}

机构：

[1] Univ Jena, Dept Pharmaceut Biol, Hans Knoll Inst, D-07745 Jena, Germany

[2] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, D-07745 Jena, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 07期

关键词：

Armillaria; Melleolide; Antibiotics; Natural product; Cytotoxicity; SECONDARY MOLD METABOLITES; ARMILLARIA-MELLEA; ANTITUMOR AGENT; ARYL ESTERS; IROFULVEN; CULTURES; REPAIR; CELLS;

D O I：

10.1016/j.bmcl.2011.02.026

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Melleolide sesquiterpene aryl esters are secondary products of the mushroom genus Armillaria. We compared the cytotoxicity of eleven melleolides-five thereof are new natural products-against four human cancer cell lines. Armillaridin, 4-O-methylarmillaridin, and dehydroarmillylorsellinate were most active, at IC50 = 3.0, 4.1 and 5.0 mu M, respectively, against Jurkat T cells for the former two compounds, and K-562 cells for the latter. Dehydroarmillylorsellinate did not inhibit respiration and RNA-synthesis of K-562 cells at 5 mu M. However, replication of DNA dropped to 35% after 120 min at this concentration, and translational activity also decreased. (C) 2011 Published by Elsevier Ltd.

引用

页码：2003 / 2006

页数：4

共 17 条

[1] SECONDARY MOLD METABOLITES .14. STRUCTURES OF MELLOLIDES-B-D, 3 ANTIBACTERIAL SESQUITERPENOIDS FROM ARMILLARIA-MELLEA [J].

ARNONE, A ;

CARDILLO, R ;

NASINI, G .

PHYTOCHEMISTRY, 1986, 25 (02) :471-474

[2]

ARNONE A, 1988, GAZZ CHIM ITAL, V118, P523

[3] ISOLATION AND STRUCTURE (X-RAY-ANALYSIS) OF THE ORSELLINATE OF ARMILLOL, A NEW ANTIBACTERIAL METABOLITE FROM ARMILLARIA-MELLEA [J].

DONNELLY, D ;

SANADA, S ;

OREILLY, J ;

POLONSKY, J ;

PRANGE, T ;

PASCARD, C .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1982, (02) :135-137

[4] ARMILLANE, A SATURATED SESQUITERPENE ESTER FROM ARMILLARIA-MELLEA [J].

DONNELLY, DMX ;

HUTCHINSON, RM .

PHYTOCHEMISTRY, 1990, 29 (01) :179-182

[5] SESQUITERPENE ARYL ESTERS FROM ARMILLARIA-MELLEA [J].

DONNELLY, DMX ;

HUTCHINSON, RM ;

COVENEY, D ;

YONEMITSU, M .

PHYTOCHEMISTRY, 1990, 29 (08) :2569-2572

[6] Influence of irofulven, a transcription-coupled repair-specific antitumor agent, on RNA polymerase activity, stability and dynamics in living mammalian cells [J].

Escargueil, Alexandre E. ;

Poindessous, Virginie ;

Soares, Daniele Grazziotin ;

Sarasin, Alain ;

Cook, Peter R. ;

Larsen, Annette K. .

JOURNAL OF CELL SCIENCE, 2008, 121 (08) :1275-1283

[7] Anti-tumour compounds illudin S and Irofulven induce DNA lesions ignored by global repair and exclusively processed by transcription- and replication-coupled repair pathways [J].

Jaspers, NGJ ;

Raams, A ;

Kelner, MJ ;

Ng, JMY ;

Yamashita, YM ;

Takeda, S ;

McMorris, TC ;

Hoeijmakers, JHJ .

DNA REPAIR, 2002, 1 (12) :1027-1038

[8] Profiling patterns of glutathione reductase inhibition by the natural product illudin S and its acylfulvene analogues [J].

Liu, Xiaodan ;

Sturla, Shana J. .

MOLECULAR BIOSYSTEMS, 2009, 5 (09) :1013-1024

[9] Structure-activity studies of antitumor agent irofulven (hydroxymethylacylfulvene) and analogues [J].

McMorris, TC ;

Yu, J ;

Lira, R ;

Dawe, R ;

MacDonald, JR ;

Waters, SJ ;

Estes, LA ;

Kelner, MJ .

JOURNAL OF ORGANIC CHEMISTRY, 2001, 66 (18) :6158-6163

[10] MELLEOLIDE, A NEW ANTIBIOTIC FROM ARMILLARIA-MELLEA [J].

MIDLAND, SL ;

IZAC, RR ;

WING, RM ;

ZAKI, AI ;

MUNNECKE, DE ;

SIMS, JJ .

TETRAHEDRON LETTERS, 1982, 23 (25) :2515-2518

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