Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum

Lin Du; Andrew J. Robles; Jarrod B. King; Susan L. Mooberry; Robert H. Cichewicz

doi:10.1021/np5002253

Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum

Lin Du, Andrew J. Robles, Jarrod B. King, Susan L. Mooberry, Robert H. Cichewicz

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1459-1466
Number of pages	8
Journal	Journal of Natural Products
Volume	77
Issue number	6
DOIs	https://doi.org/10.1021/np5002253
State	Published - Jun 27 2014

ASJC Scopus subject areas

Analytical Chemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine
Organic Chemistry

Access to Document

10.1021/np5002253

Cite this

@article{5f6d22fa243f4e8ba7a1dfd995492f87,

title = "Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum",

abstract = "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.",

author = "Lin Du and Robles, {Andrew J.} and King, {Jarrod B.} and Mooberry, {Susan L.} and Cichewicz, {Robert H.}",

year = "2014",

month = jun,

day = "27",

doi = "10.1021/np5002253",

language = "English (US)",

volume = "77",

pages = "1459--1466",

journal = "Journal of Natural Products",

issn = "0163-3864",

publisher = "American Chemical Society",

number = "6",

}

TY - JOUR

T1 - Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum

AU - Du, Lin

AU - Robles, Andrew J.

AU - King, Jarrod B.

AU - Mooberry, Susan L.

AU - Cichewicz, Robert H.

PY - 2014/6/27

Y1 - 2014/6/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84903649298&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84903649298&partnerID=8YFLogxK

U2 - 10.1021/np5002253

DO - 10.1021/np5002253

M3 - Article

C2 - 24893224

AN - SCOPUS:84903649298

SN - 0163-3864

VL - 77

SP - 1459

EP - 1466

JO - Journal of Natural Products

JF - Journal of Natural Products

IS - 6

ER -

Cytotoxic dimeric epipolythiodiketopiperazines from the ascomycetous fungus Preussia typharum

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this