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. 2017 Feb 24;80(2):427-433.
doi: 10.1021/acs.jnatprod.6b00960. Epub 2017 Jan 31.

Chlorinated Dehydrocurvularins and Alterperylenepoxide A from Alternaria sp. AST0039, a Fungal Endophyte of Astragalus lentiginosus

Bharat P Bashyal  1 , E M Kithsiri Wijeratne  1 , Joseph Tillotson  2 , A Elizabeth Arnold  3 , Eli Chapman  2 , A A Leslie Gunatilaka  1
Affiliations

Chlorinated Dehydrocurvularins and Alterperylenepoxide A from Alternaria sp. AST0039, a Fungal Endophyte of Astragalus lentiginosus

Bharat P Bashyal et al. J Nat Prod. .

Abstract

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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Conflict of interest statement

Notes

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Selected 1H–1H COSY and HMBC correlations for 1 and 4.
Figure 2
Figure 2
Selected NOE correlations for 4.
Figure 3
Figure 3
Cell-based heat-shock induction assay data for dehydrocurvularins (1–3), monocillin I (MON, positive control), and DMSO (negative control). (A) Data for 1 and 2 at 5.00 μM, 3 at 5.00 μM (3A), 2.50 μM (3B), and 1.25 μM (3C), and MON at 0.50 μM expressed as a percentage of the negative control (DMSO). (B) Concentration-dependent heat-shock induction for MON and 3 [dehydrocurvularin]; relative fluorescence units per well were determined as a measure of heat-shock reporter activation. For both experiments, the mean and standard deviation of triplicate determinations are presented, and the results are representative of three independent experiments.
Figure 4
Figure 4
Induction of UPR by dehydrocurvularins 1–3. MDB-MA-231 cells were treated with indicated concentrations (μM) of 1–3 for 8 h. The proteins XBP1, ATF4, and CHOP were analyzed by immunoblot. DMSO and CB-5083 (C; 1.0 μM) were used as negative and positive controls, respectively. The known proteasome inhibitor MG132 (M; 5.0 μM) was included for comparison purposes, and β-actin (Actin) was used as a loading control.
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References

    1. Gunatilaka AAL. J Nat Prod. 2006;69:509–526. - PMC - PubMed
    2. Kusari S, Spiteller M. Nat Prod Rep. 2011;28:1203–1207. - PubMed
    1. Dai C, Whitesell L, Rogers AB, Lindquist S. Cell. 2007;130:1005–1018. - PMC - PubMed
    2. Santagata S, Xu Y, Wijeratne EMK, Kontnik R, Rooney C, Perley CC, Kwon H, Clardy J, Kesari S, Whitesell L, Lindquist S, Gunatilaka AAL. ACS Chem Biol. 2012;7:340–349. - PMC - PubMed
    1. Turbyville TJ, Wijeratne EMK, Liu MX, Burns AM, Seliga CJ, Luevano LA, David CL, Feath SH, Whitesell L, Gunatilaka AAL. J Nat Prod. 2006;69:178–184. - PMC - PubMed
    2. McLellan CA, Turbyville TJ, Wijeratne EMK, Kerschen A, Vierling E, Queitsch C, Whitesell L, Gunatilaka AAL. Plant Physiol. 2007;145:174–182. - PMC - PubMed
    1. Findlay JA, Kwan D. Can J Chem. 1973;51:1617–1619.
    2. Jordan DB, Zheng YJ, Lockett BA, Basarab GS. Biochemistry. 2000;39:2276–2282. - PubMed
    1. Nukina M, Marumo S. Agric Biol Chem. 1977;41:717.

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