Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert

E. M Kithsiri Wijeratne, Thomas J. Turbyville, Zhongge Zhang, Donna Bigelow, Leland S. Pierson, Hans D. VanEtten, Luke Whitesell, Louise M. Canfield, Leslie Gunatilaka

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)-dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)-terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7), and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid-catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)-terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were elucidated by spectroscopic methods. All compounds were evaluated for cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460 cell line indicated that 4 is capable of disrupting the cell cycle through an apparent arrest to progression at the G1 and G 2/M phases in this p53 competent cell line. A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed.

Original languageEnglish (US)
Pages (from-to)1567-1573
Number of pages7
JournalJournal of Natural Products
Volume66
Issue number12
DOIs
StatePublished - Dec 2003

Fingerprint

Opuntia
Aspergillus terreus
Sonoran Desert
Rhizosphere
Aspergillus
rhizosphere
Cells
acids
Cell Line
Acids
Cell Cycle
cell lines
Hydrogenation
Biosynthetic Pathways
cell cycle
Non-Small Cell Lung Carcinoma
Glioma
Biological Assay
Cell Division
Methylation

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Wijeratne, E. M. K., Turbyville, T. J., Zhang, Z., Bigelow, D., Pierson, L. S., VanEtten, H. D., ... Gunatilaka, L. (2003). Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert. Journal of Natural Products, 66(12), 1567-1573. https://doi.org/10.1021/np030266u

Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert. / Wijeratne, E. M Kithsiri; Turbyville, Thomas J.; Zhang, Zhongge; Bigelow, Donna; Pierson, Leland S.; VanEtten, Hans D.; Whitesell, Luke; Canfield, Louise M.; Gunatilaka, Leslie.

In: Journal of Natural Products, Vol. 66, No. 12, 12.2003, p. 1567-1573.

Research output: Contribution to journalArticle

Wijeratne, EMK, Turbyville, TJ, Zhang, Z, Bigelow, D, Pierson, LS, VanEtten, HD, Whitesell, L, Canfield, LM & Gunatilaka, L 2003, 'Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert', Journal of Natural Products, vol. 66, no. 12, pp. 1567-1573. https://doi.org/10.1021/np030266u
Wijeratne, E. M Kithsiri ; Turbyville, Thomas J. ; Zhang, Zhongge ; Bigelow, Donna ; Pierson, Leland S. ; VanEtten, Hans D. ; Whitesell, Luke ; Canfield, Louise M. ; Gunatilaka, Leslie. / Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert. In: Journal of Natural Products. 2003 ; Vol. 66, No. 12. pp. 1567-1573.
@article{c9f35f6a2b1b405ba6bc8ddcfdc78420,
title = "Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert",
abstract = "A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)-dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)-terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7), and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid-catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)-terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were elucidated by spectroscopic methods. All compounds were evaluated for cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460 cell line indicated that 4 is capable of disrupting the cell cycle through an apparent arrest to progression at the G1 and G 2/M phases in this p53 competent cell line. A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed.",
author = "Wijeratne, {E. M Kithsiri} and Turbyville, {Thomas J.} and Zhongge Zhang and Donna Bigelow and Pierson, {Leland S.} and VanEtten, {Hans D.} and Luke Whitesell and Canfield, {Louise M.} and Leslie Gunatilaka",
year = "2003",
month = "12",
doi = "10.1021/np030266u",
language = "English (US)",
volume = "66",
pages = "1567--1573",
journal = "Journal of Natural Products",
issn = "0163-3864",
publisher = "American Chemical Society",
number = "12",

}

TY - JOUR

T1 - Cytotoxic Constituents of Aspergillus terreus from the Rhizosphere of Opuntia versicolor of the Sonoran Desert

AU - Wijeratne, E. M Kithsiri

AU - Turbyville, Thomas J.

AU - Zhang, Zhongge

AU - Bigelow, Donna

AU - Pierson, Leland S.

AU - VanEtten, Hans D.

AU - Whitesell, Luke

AU - Canfield, Louise M.

AU - Gunatilaka, Leslie

PY - 2003/12

Y1 - 2003/12

N2 - A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)-dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)-terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7), and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid-catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)-terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were elucidated by spectroscopic methods. All compounds were evaluated for cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460 cell line indicated that 4 is capable of disrupting the cell cycle through an apparent arrest to progression at the G1 and G 2/M phases in this p53 competent cell line. A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed.

AB - A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)-dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)-terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7), and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid-catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)-terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were elucidated by spectroscopic methods. All compounds were evaluated for cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460 cell line indicated that 4 is capable of disrupting the cell cycle through an apparent arrest to progression at the G1 and G 2/M phases in this p53 competent cell line. A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed.

UR - http://www.scopus.com/inward/record.url?scp=0347656928&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0347656928&partnerID=8YFLogxK

U2 - 10.1021/np030266u

DO - 10.1021/np030266u

M3 - Article

C2 - 14695798

AN - SCOPUS:0347656928

VL - 66

SP - 1567

EP - 1573

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 12

ER -