Anti-inflammatory meroterpenoids from the mangrove endophytic fungus Talaromyces amestolkiae YX1
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.
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 (1–4), along with three known compounds 5–7 (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 (1–4), 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 (1–4), along with three known compounds (5–7) on wheat solid-substrate medium culture. The absolute configuration of 1−5 (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.
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S.C. and M.D. contributed equally.