TY - JOUR
T1 - Chlorinated Dehydrocurvularins and Alterperylenepoxide A from Alternaria sp. AST0039, a Fungal Endophyte of Astragalus lentiginosus
AU - Bashyal, Bharat P.
AU - Wijeratne, E. M.Kithsiri
AU - Tillotson, Joseph
AU - Arnold, A. Elizabeth
AU - Chapman, Eli
AU - Gunatilaka, A. A.Leslie
N1 - Funding Information: Financial support for this work was provided by Grant R01 CA090265 funded by the National Cancer Institute (NCI, NIH) and Grant P41 GM094060 funded by National Institute of General Medical Sciences (NIGMS, NIH). We thank Drs. L. Whitesell and S. Santagata of Whitehead Institute for some heat-shock induction assay data and useful discussions, Prof. M. C. F. Oliveira of Universidade Federal do Ceará, Brazil, for some HRMS data, and Ms. P. Espinosa-Artiles and Ms. M. X. Liu for their help with large-scale culturing of the fungus and for conducting heat-shock induction and cytotoxicity assays. Publisher Copyright: © 2017 The American Chemical Society and American Society of Pharmacognosy.
PY - 2017/2/24
Y1 - 2017/2/24
N2 - Investigation of Alternaria sp. AST0039, an endophytic fungus obtained from the leaf tissue of Astragalus lentiginosus, led to the isolation of (−)-(10E,15S)-4,6-dichloro-10(11)-dehydrocurvularin (1), (−)-(10E,15S)-6-chloro-10(11)-dehydrocurvularin (2), (−)-(10E,15S)-10(11)-dehydrocurvularin (3), and alterperylenepoxide A (4) together with scytalone and α-acetylorcinol. Structures of 1 and 4 were established from their spectroscopic data, and the relative configuration of 4 was determined with the help of nuclear Overhauser effect difference data. All metabolites were evaluated for their cytotoxic activity and ability to induce heat-shock and unfolded protein responses. Compounds 2 and 3 exhibited cytotoxicity to all five cancer cell lines tested and increased the level of the pro-apoptotic transcription factor CHOP, but only 3 induced the heat-shock response and caused a strong unfolded protein response.
AB - Investigation of Alternaria sp. AST0039, an endophytic fungus obtained from the leaf tissue of Astragalus lentiginosus, led to the isolation of (−)-(10E,15S)-4,6-dichloro-10(11)-dehydrocurvularin (1), (−)-(10E,15S)-6-chloro-10(11)-dehydrocurvularin (2), (−)-(10E,15S)-10(11)-dehydrocurvularin (3), and alterperylenepoxide A (4) together with scytalone and α-acetylorcinol. Structures of 1 and 4 were established from their spectroscopic data, and the relative configuration of 4 was determined with the help of nuclear Overhauser effect difference data. All metabolites were evaluated for their cytotoxic activity and ability to induce heat-shock and unfolded protein responses. Compounds 2 and 3 exhibited cytotoxicity to all five cancer cell lines tested and increased the level of the pro-apoptotic transcription factor CHOP, but only 3 induced the heat-shock response and caused a strong unfolded protein response.
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U2 - 10.1021/acs.jnatprod.6b00960
DO - 10.1021/acs.jnatprod.6b00960
M3 - Article
C2 - 28139929
SN - 0163-3864
VL - 80
SP - 427
EP - 433
JO - Journal Of Natural Products
JF - Journal Of Natural Products
IS - 2
ER -