Cytotoxic sesquiterpenes from the endophytic fungus Pseudolagarobasidium acaciicola
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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