Cytotoxic epipolythiodioxopiperazine alkaloids from filamentous fungi of the Bionectriaceae

被引：50

作者：

Figueroa, Mario ^{[1
]}

Graf, Tyler N. ^{[1
]}

Ayers, Sloan ^{[1
]}

Adcock, Audrey F. ^{[2
]}

Kroll, David J. ^{[2
]}

Yang, Jilai ^{[3
]}

Swanson, Steven M. ^{[3
]}

Munoz-Acuna, Ulyana ^{[4
,5
]}

de Blanco, Esperanza J. Carcache ^{[4
,5
]}

Agrawal, Rajesh ^{[6
]}

Wani, Mansukh C. ^{[7
]}

Darveaux, Blaise A. ^{[8
]}

Pearce, Cedric J. ^{[8
]}

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 USA

[3] Univ Illinois, Dept Med Chem & Pharmacognosy, Chicago, IL USA

[4] Ohio State Univ, Coll Pharm, Div Pharm Practice & Adm, Columbus, OH 43210 USA

[5] Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA

[6] Univ Colorado Denver, Sch Pharm, Dept Pharmaceut Sci, Aurora, CO USA

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

[8] Mycosynthetix Inc, Hillsborough, NC USA

来源：

JOURNAL OF ANTIBIOTICS | 2012年 / 65卷 / 11期

基金：

美国国家卫生研究院;

关键词：

cytotoxicity; epipolythiodioxopiperazine alkaloids; EGFR; fungus; NF-kappa B; VERTICILLIN; METABOLITES; CELL; EPIDITHIODIOXOPIPERAZINES; INDUCTION; COMPOUND; ISOLATE; CANCER;

D O I：

10.1038/ja.2012.69

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Bioactivity-directed fractionation of the organic extracts of two filamentous fungi of the Bionectriaceae, strains MSX 64546 and MSX 59553 from the Mycosynthetix library, led to the isolation of a new dimeric epipolythiodioxopiperazine alkaloid, verticillin H (1), along with six related analogs, Sch 52900 (2), verticillin A (3), gliocladicillin C (4), Sch 52901 (5), 11'-deoxyverticillin A (6) and gliocladicillin A (7). The structures of compounds 1-7 were determined by extensive NMR and HRMS analyses, as well as by comparisons to the literature. All compounds (1-7) were evaluated for cytotoxicity against a panel of human cancer cell lines, displaying IC50 values ranging from 1.2 mu M to 10 nM. Compounds 1-5 were examined for activity in the NF-kappa B assay, where compounds 2 and 3 revealed activity in the sub-micromolar range. Additionally, compounds 1, 3 and 4 were tested for EGFR inhibition using an enzymatic assay, while compound 3 was examined against an overexpressing EGFR(+ve) cancer cell line. The Journal of Antibiotics (2012) 65, 559-564; doi: 10.1038/ja.2012.69; published online 12 September 2012

引用

页码：559 / 564

页数：6

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