A new antiviral 14-nordrimane sesquiterpenoid from an endophytic fungus Phoma sp.
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 δH 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.
References (36)
- et al.
Screening for metabolites from Penicillium novae-zeelandiae displaying radical-scavenging activity and oxidative mutagenicity: isolation of gentisyl alcohol
Mutat. Res.
(2003) - et al.
A new sesquiterpene from the endophytic fungus Nigrospora sphaerica #003
Rec. Nat. Prod.
(2016) - et al.
Chenopodolans A-C: phytotoxic furopyrans produced by Phoma chenopodiicola, a fungal pathogen of Chenopodium album
Phytochemistry
(2013) - et al.
Three new drimane sesquiterpenoids from cultures of the fungus Penicillium sp
J. Asian Nat. Prod. Res.
(2017) - et al.
Drimane-type sesqui- and norsesquiterpenoids from Polygonum hydropiper
Phytochemistry
(1985) - et al.
An epigenetic modifier induces production of (10’S)-verruculide B, an inhibitor of protein tyrosine phosphatases by Phoma sp. nov. LG0217, a fungal endophyte of Parkinsonia microphylla
Bioorg. Med. Chem.
(2017) - et al.
Seven new drimane-type sesquiterpenoids from cultures of fungus Laetiporus sulphureus
Fitoterapia
(2015) - et al.
The anti-arthritic effects of Aconitum vilmorinianum, a folk herbal medicine in Southwestern China
J. Ethnopharmacol.
(2013) - et al.
Homoisoflavonoids and xanthones from the tubers of wild and in vitro regenerated Ledebouria graminifolia and cytotoxic activities of some of the homoisoflavonoids
Phytochemistry
(2003) - et al.
α-Pyrone derivatives with cytotoxic activities, from the endophytic fungus Phoma sp. YN02-P-3
Bioorg. Med. Chem. Lett.
(2017)
Drimane-type sesquiterpenoids from the liverwort Diplophyllum serrulatum
Phytochemistry
Polyketides with antimicrobial activity from the solid culture of an endolichenic fungus Ulocladium sp
Fitoterapia
Drimane-type sesquiterpenoids from cultures of the fungus Xylaria polymorpha
Phytochem. Lett.
Diterpenoid alkaloids from Aconitum vilmorinianum
Phytochemistry
Antiviral anthraquinones and azaphilones produced by an endophytic fungus Nigrospora sp. from Aconitum carmichaeli
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.
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These authors contributed equally to this work.