Cytotoxic Dimeric Epipolythiodiketopiperazines from the Ascomycetous Fungus Preussia typharum

被引：25

作者：

Du, Lin ^{[1
,3
,5
]}

Robles, Andrew J. ^{[2
,4
,5
]}

King, Jarrod B. ^{[1
,2
,3
]}

Mooberry, Susan L. ^{[2
,4
,6
]}

Cichewicz, Robert H. ^{[1
,2
,3
]}

机构：

[1] Univ Oklahoma, Stephenson Life Sci Res Ctr, Nat Prod Discovery Grp, Norman, OK 73069 USA

[2] Univ Oklahoma, Stephenson Life Sci Res Ctr, Inst Nat Prod Applicat & Res Technol, Norman, OK 73069 USA

[3] Univ Oklahoma, Stephenson Life Sci Res Ctr, Dept Chem & Biochem, Norman, OK 73069 USA

[4] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA

[5] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA

[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA

来源：

JOURNAL OF NATURAL PRODUCTS | 2014年 / 77卷 / 06期

基金：

美国国家卫生研究院;

关键词：

DESIGNATED NCI/ADR-RES; HUMAN COLON-CARCINOMA; IN-VIVO ACTIVITY; TUMOR-GROWTH; HUMAN-BREAST; CELL-LINE; RESISTANCE; CHAETOCIN; INHIBITOR; ALKALOIDS;

D O I：

10.1021/np5002253

中图分类号：

Q94 [植物学];

学科分类号：

071001 [植物学];

摘要：

Two new dimeric epipolythiodiketopiperazines, preussiadins A (1) and B (2), together with two known diastereomers, leptosins C (6) and A (7), were obtained from the mycelia of a Preussia typharum isolate. The structures of the new compounds were established by spectroscopic methods, and the absolute configurations of 1 and 2 were assigned by chemical transformations and comparisons of quantum chemical ECD and VCD calculations to experimental data. Compound 1 exhibited potent cytotoxic activity in the NCI-60 cell line panel with an average LC50 value of 251 nM. Further studies demonstrated that 1 circumvents P-glycoprotein-mediated drug resistance, yet had no significant antitumor activity in a xenograft UACC-62 melanoma model.

引用

页码：1459 / 1466

页数：8

共 36 条

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