Benzoquinones and Terphenyl Compounds As Phosphodiesterase-4B Inhibitors from a Fungus of the Order Chaetothyriales (MSX 47445)

被引：42

作者：

El-Elimat, Tamam ^{[1
]}

Figueroa, Mario ^{[1
]}

Raja, Huzefa A. ^{[1
]}

Graf, Tyler N. ^{[1
]}

Adcock, Audrey F. ^{[2
]}

Kroll, David J. ^{[2
]}

Day, Cynthia S. ^{[3
]}

Wani, Mansukh C. ^{[4
]}

Pearce, Cedric J. ^{[5
]}

Oberlies, Nicholas H. ^{[1
]}

机构：

[1] Univ N Carolina, Dept Chem & Biochem, Greensboro, NC 27402 USA

[2] N Carolina Cent Univ, Dept Pharmaceut Sci, BRITE, Durham, NC 27707 USA

[3] Wake Forest Univ, Dept Chem, Winston Salem, NC 27109 USA

[4] Res Triangle Inst, Nat Prod Lab, Res Triangle Pk, NC 27709 USA

[5] Mycosynthetix Inc, Hillsborough, NC 27278 USA

来源：

JOURNAL OF NATURAL PRODUCTS | 2013年 / 76卷 / 03期

基金：

美国国家卫生研究院;

关键词：

BRAIN-TUMORS; DOCKING; HYPOCREALES; METABOLITES; CELL; AMP;

D O I：

10.1021/np300749w

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

Three bioactive compounds were isolated from an organic extract of an ascomycete fungus of the order Chaetothyriales (MSX 47445) using bioactivity-directed fractionation as part of a search for anticancer leads from filamentous fungi. Of these, two were benzoquinones [betulinan A (1) and betulinan C (3)), and the third was a terphenyl compound, BTH-I10204-207:A (2). The structures were elucidated using a set of spectroscopic and spectrometric techniques; the structure of the new compound (3) was confirmed via single-crystal X-ray diffraction. Compounds 1-3 were evaluated for cytotoxicity against a human cancer cell panel, for antimicrobial activity against Staphylococcus aureus and Candida albicans, and for phosphodiesterase (PDE4B2) inhibitory activities. The putative binding mode of 1-3 with PDE4B2 was examined using a validated docking protocol, and the binding and enzyme inhibitory activities were correlated.

引用

页码：382 / 387

页数：6

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