Elsevier

Phytochemistry

Volume 146, February 2018, Pages 8-15
Phytochemistry

Anti-inflammatory meroterpenoids from the mangrove endophytic fungus Talaromyces amestolkiae YX1

https://doi.org/10.1016/j.phytochem.2017.11.011Get rights and content

Highlights

  • Four previously undescribed meroterpenoids, amestolkolides A−D were isolated from Talaromyces amestolkiae YX1.

  • Their plausible and distinct biosynthetic pathways were proposed.

  • This series of meroterpenoids were firstly isolated from the fungi in the genus Talaromyces.

  • Amestolkolides B showed strong anti-inflammatory activity with IC50 values of 1.6 ± 0.1 μM in vitro.

Abstract

Four previously undescribed meroterpenoids, amestolkolides A−D, along with three known compounds were isolated from the mangrove endophytic fungus Talaromyces amestolkiae YX1 cultured on wheat solid-substrate medium culture. Their structures were elucidated by a combination of spectroscopic analyses. The absolute configurations of amestolkolides B and C, and purpurogenolide E were determined by single-crystal X-ray diffraction using Cu Kα radiation, and those of amestolkolides A and D were elucidated on the basis of experimental and calculated electronic circular dichroism spectra. The absolute configuration of amestolkolides A-D, and purpurogenolide E (9R) at C-9 was different from that of analogues (9S) in references, so that their plausible and distinct biosynthetic pathways were proposed. Amestolkolide B showed strong anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide activated in RAW264.7 cells with IC50 value of 1.6 ± 0.1 μM.

Graphical abstract

Four previously undescribed meroterpenoids, amestolkolides A−D, were isolated from the mangrove endophytic fungus Talaromyces amestolkiae YX1. Amestolkolide B showed strong anti-inflammatory activity with IC50 value of 1.6 ± 0.1 μM.

Image 1
  1. Download : Download high-res image (405KB)
  2. Download : Download full-size image

Introduction

Meroterpenoids were hybrid natural products partially derived from mevalonic acid pathways and widely derived from animals, plants, bacteria, and fungi (Geris and Simpson, 2009, Matsuda and Abe, 2015). The meroterpenoids with the source of fungi exhibited diverse structural features and a wide range of biological activities, such as asperterpenes A and B with promising inhibitory activities against BACE1 (Qi et al., 2016), austalides with strong inhibition of endo-1,3-β-D-glucanase (Zhuravleva et al., 2014), mycophenolic acid as a strong inhibitor of inosine 5′-monophosphate dehydrogenase (IMPDH) (Sintchak et al., 1996), territrem B as a potent inhibitor of acetylcholinesterase (AChE) (Peng, 1995), berkeleyacetal C exhibited promising anti-inflammatory activity (Etoh et al., 2013). Among them, berkeleyacetals are the polyketide-terpenoid hybrid meroterpenoid class, possessing a unique and congested polycyclic skeleton with 6/7/6/5/6 system. Since paraherquonin was isolated from Penicillium paraherquei in 1983 (Okuyama et al., 1983), about 13 analogues, berkeleyacetals A−C (Stierle et al., 2007), miniolutelides A−B (Iida et al., 2008), 4,25-dehydrominiolutelide B, 4,25-dehydro-22-deoxyminiolutelide B, isominiolutelide A (Zhang et al., 2012), and purpurogenolides A−E (Sun et al., 2016) have been discovered mainly several fungi in the genus Penicillium (Li et al., 2014).

The genus Talaromyces was widespread around plants, foods, soil, as well as sponges (Zhai et al., 2016). The fungus could produce a wide range of secondary metabolites, such as anthraquinones (Bara et al., 2013), prenylated indole alkaloids (Chu et al., 2010), norsesquiterpene peroxides (Li et al., 2011), sesquiterpene lactones (Ngokpol et al., 2015), and meroterpenoids (Kaur et al., 2016).

Endophytic fungi have been demonstrated to be an important source of pharmacologically active metabolites (Debbab et al., 2013). In the last decade, our research group has focused on the mangrove endophytic fungi isolated from the South China Sea to discover novel and bioactive compounds (Chen et al., 2016a, Chen et al., 2016b, Chen et al., 2017a, Chen et al., 2017b, Li et al., 2011, Liu et al., 2016, Tan et al., 2016, Xiao et al., 2013). Talaromyces amestolkiae YX1 was cultured on solid wheat medium, which led to obtain four previously undescribed meroterpenoids, amestolkolides A−D (14), along with three known compounds 57 (Fig. 1). Amestolkolides A and B (1 and 2) exhibited anti-inflammatory activity in vitro by inhibiting nitric oxide (NO) production in lipopolysaccharide activated in RAW264.7 cells with IC50 values of 30 ± 1.2 and 1.6 ± 0.1 μM, respectively. The isolation, structure elucidation, plausible biosynthetic pathways, and bioactivities of the isolates from the fungus are described herein.

Section snippets

Results and discussion

The mangrove endophytic fungus Talaromyces amestolkiae YX1 were cultured on solid wheat medium with artificial seawater for 28 days, respectively. The EtOAc extract of the wheat fermentation was fractionated by repeated silica gel chromatography and Sephadex LH-20 column chromatography to afford four previously undescribed meroterpenoids, amestolkolides A−D (14), together with three known meroterpenoids, purpurogenolide E (5) (Sun et al., 2016), chrodrimanin B (6) (Wei et al., 2011), and

Conclusions

The chemical investigation of the mangrove endophytic fungus Talaromyces amestolkiae YX1 afforded four previously undescribed meroterpenoids, amestolkolides A−D (14), along with three known compounds (57) on wheat solid-substrate medium culture. The absolute configuration of 15 (9R) at C-9 was different from that of analogues (9S) in references, it was speculated that the key epimerization of intermediate I would make the distinct biosynthetic pathways. Compounds 1–5 belonged to

General experimental procedures

Melting points were recorded on a Fisher-Johns hot-stage apparatus and were uncorrected. Optical rotations were measured on a MCP 300 (Anton Paar) polarimeter at 28 °C. UV data were recorded with MeOH as the solvent using a PERSEE TU-1900 spectrophotometer, and ECD data were obtained on a Chirascan™ CD spectrometer (Applied Photophysics). IR spectra were carried out on a Nicolet Nexus 670 spectrophotometer, in KBr discs. All NMR experiments were performed on a Bruker Avance 500 spectrometer (1H

Notes

The authors declare no competing financial interest.

Acknowledgements

We thank the National Natural Science Foundation of China (21472251, 41276146, 41404134), the Science & Technology Plan Project of Guangdong Province of China (2013B021100011), the Key project of Natural Science Foundation of Guangdong Province (2016A040403091), Special Financial Fund of Innovative Development of Marine Economic Demonstration Project (GD2012-D01-001) for generous support.

References (32)

  • S. Chen et al.

    Talaramide A, an unusual alkaloid from the mangrove endophytic fungus Talaromyces sp (HZ-YX1) as an inhibitor of mycobacterial PknG

    New J. Chem.

    (2017)
  • S. Chen et al.

    Isocoumarins and benzofurans from the mangrove endophytic fungus Talaromyces amestolkiae possess α-glucosidase inhibitory and antibacterial activities

    Rsc Adv.

    (2016)
  • Y.S. Chu et al.

    Isolation of putative biosynthetic intermediates of prenylated indole alkaloids from a thermophilic fungus Talaromyces thermophilus

    Org. Lett.

    (2010)
  • A. Debbab et al.

    Mangrove derived fungal endophytes–a chemical and biological perception

    Fungal Divers

    (2013)
  • H. Flack et al.

    The use of X-ray crystallography to determine absolute configuration

    Chirality

    (2008)
  • R. Geris et al.

    Meroterpenoids produced by fungi

    Nat. Prod. Rep.

    (2009)
  • Cited by (63)

    • Marine pharmacology in 2018: Marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action

      2022, Pharmacological Research
      Citation Excerpt :

      Additional marine natural products (62–65) listed in Table 2 and shown Fig. 2, demonstrated antidiabetic activity during 2018, but the mechanism of action of these compounds remained undetermined at the time of publication: two new butanolide derivatives asperteretal D (61) and E (62) obtained from the marine sponge Phakellia fusca-derived fungus Aspergillus terreus [92]; a novel polyketide depsidone botryorhodine H (63) isolated from a Chinese mangrove Clerodendrum inerme-derived endophytic fungus Trichoderma sp. strain 307, that exhibited significant α-glucosidase inhibitory activity [93]; and, two new cembranoids (64,65) isolated from the Caribbean Sea coral Eunicea sp. that were shown to activate the proliferation of pancreatic beta-cells, a strategy that could “counteract hyperglycemia” [94]. As shown in Table 2 and Fig. 2, there was a remarkable increase in anti-inflammatory pharmacology of marine compounds [95–118] during 2018. The molecular mechanism of action of anti-inflammatory marine natural products (55, 66-78) was assessed in both in vitro and in vivo preclinical pharmacological studies in several papers which used several in vitro and in vivo models of inflammation.

    • Novel geranylhydroquinone derived meroterpenoids from the fungus Clitocybe clavipes and their cytotoxic activity

      2022, Fitoterapia
      Citation Excerpt :

      Meroterpenoids are a prominent group of natural products partially derived from terpenoid pathways [1–3]. Fungi are the outstanding and important producers of meroterpenoids, which exhibit unique chemical structures and diversity skeletons with impressive range of excellent pharmacological activities [4–8]. Notably, several fungal meroterpenoids such as mycophenolic acid [9], fumagillin [10], pyripyropene A [11], territrem B [12], ascofuranone [13] and vibralactone [14] have been reported to be as clinical drugs or promising lead compounds.

    • Azaphilone derivatives with anti-inflammatory activity from the mangrove endophytic fungus Penicillium sclerotiorum ZJHJJ-18

      2022, Bioorganic Chemistry
      Citation Excerpt :

      In previously, we characterized a series of bioactive azaphilones from Penicillium species isolated from the mangrove plant [12,14]. As part of our continuing search for new natural anti-inflammatory products from the mangrove endophytic fungi [15–18], a fungal strain Penicillium sclerotiorum ZJHJJ-18, collected from the stems of the mangrove plant Hibiscus tiliaceus, was subjected to a systematic chemical investigation which led to the isolation of twelve azaphilone derivatives (1–12), including nine new analogues, named sclerazaphilones A–J (1–9). Compounds 1–4 represent a first reported class of N-containing azaphilone analogues featuring a 5/6 dicyclic core.

    View all citing articles on Scopus
    1

    S.C. and M.D. contributed equally.

    View full text