Elsevier

Fitoterapia

Volume 83, Issue 6, September 2012, Pages 1087-1091
Fitoterapia

Heptaketides with antiviral activity from three endolichenic fungal strains Nigrospora sp., Alternaria sp. and Phialophora sp.

https://doi.org/10.1016/j.fitote.2012.05.002Get rights and content

Abstract

Two new heptaketides, (+)-(2S,3S,4aS)-altenuene (1a) and (−)-(2S,3S,4aR)-isoaltenuene (2a), together with six known compounds, (−)-(2R,3R,4aR)-altenuene (1b), (+)-(2R,3R,4aS)-isoaltenuene (2b), 5′-methoxy-6-methyl-biphenyl-3,4,3′-triol (3), alternariol (4), alternariol-9-methyl ether (5), and 4-hydroxyalternariol-9-methyl ether (6) were isolated from the EtOAc extract of an endolichenic fungal strain Nigrospora sphaerica (No.83-1-1-2). Compounds 1a and 1b were separated from enantiomers 1 by chiral HPLC, and so were 2a and 2b from enantiomers 2. Interestingly, 16 were also obtained from other two endolichenic fungal strains Alternaria alternata (No.58-8-4-1) and Phialophora sp. (No.96-1-8-1). The structures of 16 were elucidated by means of MS, HR-MS, NMR, and X-ray diffraction. Furthermore, the absolute configurations of 1a–2b were determined by CD experiments and CD calculation. Of these compounds, 4 and 5 showed antiviral activity against herpes simplex virus (HSV) in vitro, with IC50 values of 13.5 and 21.3 μM, and with selective index (SI) values of 26.5 and 17.1, respectively.

Graphical abstract

Two new heptaketides were isolated from three endolichenic fungal strains Nigrospora sp., Alternaria sp., and Phialophora sp. Their structures and antiviral activity are reported herein.

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Introduction

Endolichenic fungi are microorganisms living in the thalli of lichens, which are analogous to the plant endophytic fungi inhabiting the intercellular spaces of the hosts [1]. Up to now, only a limited number of secondary metabolites have been previously reported from the endolichenic fungi, including Corynespora sp. [1], [2], Pestalotiopsis sp. [3], Neurospora sp. [4], Coniochaeta sp. [5], [6], Ulocladium sp. [7], Xylaria sp. [8], Preussia sp. [9], and Phaeosphaeria sp. [10]. In the search for bioactive secondary metabolites from microorganisms, the EtOAc extract of an endolichenic fungus Nigrospora sphaerica (No.83-1-1-2) showed (inhibition rate (IR), 67.1%) inhibition activity against HSV at the concentration of 12.5 μg/mL. Further chemical investigation on the EtOAc extract led to the isolation of eight secondary metabolites including two new heptaketides (1a and 2a) (Fig. 1). Interestingly, these metabolites were also obtained from the EtOAc extracts of other two endolichenic fungal strains Alternaria alternata (No.58-8-4-1) and Phialophora sp. (No.96-1-8-1). Herein, we report the isolation, structure elucidation, and antiviral activity of these compounds.

Section snippets

General

Optical rotations were measured on a JASCO P-1020 digital polarimeter at room temperature. IR spectra were recorded on a JASCO FT/IR-480 plus Fourier transform infrared spectrometer. UV spectra were recorded in CH3OH using a JASCO V-550 UV/VIS spectrophotometer. CD spectra were recorded in CH3OH using a JASCO J-810 spectrophotometer at room temperature. ESI-MS was performed on a Finigan LCQ Advantage MAX mass spectrometer and HR-ESI-MS was recorded on an Agilent 6200 ESI/TOF mass spectrometer,

Results and discussion

The molecular formula of 1 was assigned as C15H16O6 (eight degrees of unsaturation) on the basis of HR-ESI-MS at m/z 293.1019 [M + H]+ (calcd. for C15H17O6, 293.1019). The 1H NMR spectrum of 1 exhibited signals for one methyl group at δH 1.47 (s), one methoxy group at δH 3.86 (s), a pair of meta-positioned aromatic protons at δH 6.50 and 6.74 (each, d, J = 2.3 Hz), an olefinic proton at δH 6.30 (d, J = 3.3 Hz), and one phenolic hydroxyl group at δH 11.30 (s). The 13C NMR spectrum combined with DEPT-135

Acknowledgments

This work was financially supported by grants from the Ministry of Science and Technology of China (2009CB522300, and 2009ZX09302-004), by the Program for New Century Excellent Talents in University (NCET-10-0120) from the Ministry of Education of China, and by the Fundamental Research Funds for the Central Universities (21611203).

References (26)

  • Q.X. Wang et al.

    Fitoterapia

    (2012)
  • G. Li et al.

    J Nat Prod

    (2012)
  • Q.C. Zhu et al.

    J Biomol Screen

    (2010)
  • H. Hussain et al.

    Biochem Syst Ecol

    (2007)
  • T. Tanahashi et al.

    Phytochemistry

    (2003)
  • P.A. Paranagama et al.

    J Nat Prod

    (2007)
  • E.M.K. Wijeratne et al.

    J Nat Prod

    (2010)
  • G. Ding et al.

    J Nat Prod

    (2009)
  • F. Zhang et al.

    J Nat Prod

    (2009)
  • Y.C. Wang et al.

    Org Lett

    (2010)
  • Y.C. Wang et al.

    J Nat Prod

    (2010)
  • W. Wu et al.

    J Nat Prod

    (2011)
  • F. Zhang et al.

    J Nat Prod

    (2012)
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    Authors contributed equally to this work.

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