A new antiviral 14-nordrimane sesquiterpenoid from an endophytic fungus Phoma sp.

doi:10.1016/j.phytol.2018.11.005

Phytochemistry Letters

Volume 29, February 2019, Pages 75-78

https://doi.org/10.1016/j.phytol.2018.11.005 Get rights and content

Highlights

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A new rare 14-nordrimane sesquiterpenoid was isolated from endophytic Phoma sp.
•
The structure was elucidated by means of spectroscopic methods.
•
Compounds 1 and 2 exhibited antiviral activity against H1N1 influenza virus.

Abstract

A new rare 14-nordrimane-type sesquiterpenoid, named phomanolide (1), together with five known compounds, (–)-6-methoxymellein (2), 7-hydroxy-3, 5-dimethyl-isochromen-1-one (3), norlichexanthone (4), 6-methylsalicylic acid (5), and gentisyl alcohol (6), were obtained from the culture broth of an endophytic fungus Phoma sp. isolated from the roots of Aconitum vilmorinianum. The structure of compound 1 was established based on extensive spectroscopic analysis. Compound 1 was the first example of 14-nordrimane-type sesquiterpene up to now. Compounds 1 and 2 showed antiviral activities against influenza A virus (A/Puerto Rico/8/34, H1N1) with IC₅₀ values of 2.96 ± 0.64 and 20.98 ± 2.66 μg/mL, respectively.

Graphical abstract

Introduction

Endophytic fungi are microorganisms residing in the tissues of their host plants and causing no apparent disease symptoms (Petrini et al., 1991). The secondary metabolites produced by endophytic fungi had been verified to possess potent bioactivities (Gao et al., 2013; Xiao et al., 2014). Among them, the genus Phoma is one of the important contributors, which could produce diverse chemical substances with many kinds of bioactivities, such as anti-herpesvirus topopyrone B (Kanai et al., 2000), phytotoxic furopyrans (Cimmino et al., 2013), antifungal macrolide pyrenophorol (Krohn et al., 2007), cytotoxic spiciferones (Tan et al., 2018) and α-pyrones (Sang et al., 2017), immunomodulatory polyketides (Sun et al., 2017), protein tyrosine phosphatase 1B (PTP1B) inhibitory biphenyl ether (Sumilat et al., 2017) and (10′S)-verruculide B (Gubiani et al., 2017). As far as we know, there was no report of anti-influenza active compound derived from Phoma in the literature.

The perennial herb Aconitum vilmorinianum has long been used as an important prescription medicine for the treatment of rheumatism and pains by natives. Some researches on chemical constituents and pharmaceutical uses of this plant had been reported previously (Yin et al., 2015; Li et al., 2013). However, very little work has been performed on the endophytic fungi of the plant till now.

Our recent research work is focused on anti-influenza screening of the endophytic fungi from medicinal plants. The culture extract of the fungal strain Phoma sp. YE3135, obtained from the roots of A. vilmorinianum, was found to possess in vitro antiviral activity against H1N1 influenza virus. The following chemical investigation on the fermentation broth of this strain resulted in a new rare 14-nordrimane-type sesquiterpenoid (1), together with five known compounds, (–)-6-methoxymellein (2) (Choudhary et al., 2004), 7-hydroxy-3, 5-dimethyl-isochromen-1-one (3) (Wang et al., 2012), norlichexanthone (4) (Mutanyatta et al., 2003), 6-methylsalicylic acid (5) (Chen at al., 2017; Mazzini et al., 2006), and gentisyl alcohol (6) (Alfaro et al., 2003) (Fig. 1). To the best of our knowledge, drimane-type sesquiterpenoid was isolated from the fungal genus of Phoma for the first time. The structure of the new compound was assigned by analysis of spectroscopic experiments. Herein, we describe the isolation, structural elucidation, and antiviral activities of the isolated compounds from this fungus.

Section snippets

Results and discussion

Compound 1 was obtained as colorless oil. Its molecular formula was determined as C₁₄H₂₀O₃ from a quasi-molecular ion peak at m/z 259.1306 [M + Na]⁺ in the HRESI-MS, indicating the existence of five degrees of unsaturation. The IR spectrum of 1 showed absorption bands for a hydroxyl group (3447 cm⁻¹), a lactone group (1752 cm⁻¹), and an exocyclic methylene group (1648 and 908 cm⁻¹). The ^lH NMR spectrum exhibited two olefinic protons at δ_H 4.89 (1H, s) and 4.74 (1H, s), two unequivalent

Conclusion

Recently, drimane sesquiterpenoids had been found in the fungal genus of Cyathus (Kou et al., 2018), Penicillium (Ding et al., 2017), Nigrospora (Chen et al., 2016), Laetiporus(He et al., 2015), Perenniporia (Kwon et al., 2018), Pleosporales (Cao et al., 2017), Pestalotiopsis (Xiao et al., 2017), and Xylaria (Yang et al., 2017). In our study, drimane sesquiterpenoid was isolated from the fungal genus of Phoma for the first time. Previously, several naturally occurring 11-nordrimane derivatives

General experimental procedures

Optical rotation was measured on a Jasco P-2000 polarimeter. IR spectrum was recorded on a Bio-Rad FTS spectrometer with KBr pellets. NMR spectra were acquired on a Bruker DRX-500 spectrometer with TMS as internal standard. HRESIMS was measured on an Agilent G3250AA LC-MSD TOF mass spectrometer. Column chromatography (CC) was employed on silica gel (200–300 mesh, Qingdao Marine Chemical Inc., China), RP-18 silica gel (40−63 μm, Merck), and Sephadex LH-20 (Pharmacia).

Fungal material

The strain YE3135 was

Acknowledgments

This work was ﬁnancially supported by the National Natural Science Foundation of China (No. 81,460,545 and 81,860,634), and Program for Excellent Young Talents, Yunnan University.

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¹: These authors contributed equally to this work.

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A new antiviral 14-nordrimane sesquiterpenoid from an endophytic fungus Phoma sp.

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Results and discussion

Conclusion

General experimental procedures

Fungal material

Acknowledgments

Mutat. Res.

Rec. Nat. Prod.

Phytochemistry

J. Asian Nat. Prod. Res.

Phytochemistry

Bioorg. Med. Chem.

Fitoterapia

J. Ethnopharmacol.

Phytochemistry

Bioorg. Med. Chem. Lett.

Phytochemistry

Fitoterapia

Phytochem. Lett.

Phytochemistry

Fitoterapia

New norsesquiterpene aldehyde and sesquiterpene hemiacetal from the seed of Polygonum hydropiper

Experientia

Drimane sesquiterpene lactones from Peniophora polygonia

Nat. Prod. Rep.

Antifungal drimane sesquiterpenoids from a marine-derived Pleosporales sp. fungus

Chem. Nat. Compd.