Cytotoxic sesquiterpenes from the endophytic fungus Pseudolagarobasidium acaciicola

doi:10.1016/j.phytochem.2015.11.016

Phytochemistry

Volume 122, February 2016, Pages 126-138

https://doi.org/10.1016/j.phytochem.2015.11.016 Get rights and content

Highlights

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Twenty compounds were isolated from the fungus Pseudolagarobasidium acaciicola.
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The fungus P. acaciicola was isolated from a mangrove tree, Bruguiera gymnorrhiza.
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An isolated terpene endoperoxide displayed potent cytotoxic activity (IC₅₀ 0.28 μM).
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The endoperoxide of sesquiterpenes has significant impact on cytotoxic activity.

Abstract

Twenty previously unknown compounds and two known metabolites, merulin A and merulin D, were isolated from the endophytic fungus Pseudolagarobasidium acaciicola, which was isolated from a mangrove tree, Bruguiera gymnorrhiza. Structures of the 20 compounds were elucidated by analysis of spectroscopic data. The absolute configuration of seven of these compounds was addressed by a single crystal X-ray analysis using CuKα radiation and an estimate of the Flack parameter. Three compounds also possessed a tricyclic ring system. Terpene endoperoxides isolated exhibited cytotoxic activity, while those without an endoperoxide moiety did not show activity. The endoperoxide moiety of sesquiterpenes has significant impact on cytotoxic activity, and thus is an important functionality for cytotoxicity. One terpene endoperoxide displayed potent cytotoxic activity (IC₅₀ 0.28 μM), and selectively exhibited activity against the HL-60 cell line.

Graphical abstract

Twenty compounds were isolated from the endophytic fungus Pseudolagarobasidium acaciicola, which was isolated from a mangrove tree, Bruguiera gymnorrhiza. One terpene endoperoxide displayed potent cytotoxicity (IC₅₀ 0.28 μM), and selectively exhibited activity toward the HL-60 cell line.

Introduction

Endophytic fungi symbiotically live in plant tissues, and they are important sources of bioactive compounds (Kusari et al., 2013, Tan and Zou, 2001). Endophytic fungi from Thai medicinal plants were isolated, and chemical investigation of these fungi led to the isolation of several bioactive metabolites (Chomcheon et al., 2010, Chomcheon et al., 2009, Senadeera et al., 2012). Recently, the isolation of novel tricyclic and spirobicyclic compounds (1 and 2) and (nor)sesquiterpene endoperoxides 3–6 was communicated, i.e. merulin or steperoxide (Fig. 1), from the endophytic fungus Pseudolagarobasidium acaciicola, which was isolated from a mangrove tree, Bruguiera gymnorrhiza (Wibowo et al., 2014). Unique structures of 1 and 2 were highlighted as novel natural products isolated in 2014 (Hill and Sutherland, 2014). Herein, the isolation and cytotoxic activity of twenty new compounds (7–26) and two known sesquiterpenes 27 and 28 from the endophytic fungus P. acaciicola are reported.

Section snippets

Structure elucidation of new fungal metabolites (7–26)

Isolation of a broth extract of the fungus P. acaciicola gave twenty new compounds (7–26), together with known metabolites, merulin A or steperoxide B (27) and merulin D (28) (Chokpaiboon et al., 2011, Chokpaiboon et al., 2010, Li et al., 2011, Liu et al., 2010).

Acaciicolide A (7), C₁₅H₂₂O₃, had an IR absorption 1716 cm⁻¹ of a carbonyl group. The ¹H NMR spectrum of 7 exhibited signals of three singlet methyls, five methylene groups, an olefinic proton, and an oxygenated methine, while ¹³C NMR

Conclusions

In summary, new fungal metabolites (7–26), as well as known compounds (27 and 28), were isolated from the endophytic fungus P. acaciicola. Among the isolated metabolites, compounds 7–9, namely acaciicolide A–C, have a novel tricyclic ring system, while sesquiterpenes 10–21, namely acaciicolinol A–L, are 6/6 spirobicyclic compounds. Sesquiterpenes 22 and 23 have 5/6 spirobicyclic ring system, while 24–26 are derivatives of merulins. Terpene endoperoxides displayed potent cytotoxic activity, and

General experimental procedures

Melting points were recorded on Büchi 535 melting point apparatus without correction. Optical rotations were measured on a JASCO P-1020 polarimeter. UV spectra were obtained from a Shimadzu UV-1700 PharmaSpect UV–Vis spectrophotometer. IR spectra were acquired with a Perkin Elmer Spectrum ONE spectrophotometer using Attenuated Total Reflectance (ATR) technique. The NMR spectra were recorded on a Bruker Avance 300 (¹H at 300 MHz, ¹³C at 75 MHz), or Bruker AM400 (¹H at 400 MHz, ¹³C at 100 MHz), or

Acknowledgements

This work is supported by the Center of Excellence on Environmental Health and Toxicology, Science & Technology Postgraduate Education and Research Development Office (PERDO), Ministry of Education. This research is also partially supported by Mahidol University. T. Aree thanks for the financial support by the National Research University Project of Thailand (WCU-58-013-FW) and the Ratchadapisek Sompoch Endowment Fund, Chulalongkorn University (CU-58-021-FW). M. W. is grateful to the ASEAN

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View full text

Cytotoxic sesquiterpenes from the endophytic fungus Pseudolagarobasidium acaciicola

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Structure elucidation of new fungal metabolites (7–26)

Conclusions

General experimental procedures

Acknowledgements

Tetrahedron Lett.

Phytochemistry

Phytochemistry

Phytochemistry

Tetrahedron Lett.

Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells

Planta Med.

Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing

Cancer Res.

Artemisinin and its derivatives: a novel class of anti-malarial and anti-cancer agents

Chem. Soc. Rev.

Antiangiogenic effect of chamigrane endoperoxides from a Thai mangrove-derived fungus

J. Nat. Prod.

Cytotoxic nor-chamigrane and chamigrane endoperoxides from a basidiomycetous fungus

J. Nat. Prod.

Cyclopentenones, scaffolds for organic synthesis produced by the endophytic fungus, mitosporic Dothideomycete sp. LRUB20

J. Nat. Prod.

Curvularides A–E: antifungal hybrid peptide-polyketides from the endophytic fungus Curvularia geniculata

Chem. Eur. J.