Elsevier

Fitoterapia

Volume 105, September 2015, Pages 147-150
Fitoterapia

Metabolites from Combretum dolichopetalum and its associated endophytic fungus Nigrospora oryzae — Evidence for a metabolic partnership

https://doi.org/10.1016/j.fitote.2015.06.018Get rights and content

Abstract

A new altersolanol derivative, 4-dehydroxyaltersolanol A (9), along with two known sesquiterpenoids, (S)-7′-hydroxyabscisic acid (7) and (S)-abscisic acid (8) were obtained from the endophytic fungus, Nigrospora oryzae, isolated from leaves of Combretum dolichopetalum. The host plant yielded six known compounds including ellagic acid (1), 3, 3′, 4-tri-O-methylellagic acid (2), arjunolic acid (3), 4′-dihydrophaseic acid (4), echinulin (5) and arestrictin B (6). Close structural similarities with regard to compounds 4, 7 and 8 were observed between the metabolites from the host plant and those of the endophytic fungus. Furthermore compounds 5 and 6 are related to alkaloids isolated from N. oryzae previously thus stressing the notion that some of the isolated plant metabolites may actually be of fungal origin. The structures of the isolated compounds were established by spectroscopic methods including 1D, 2D NMR, MS, and by comparison with the literature. 4-Dehydroxyaltersolanol A (9) and 3, 3′, 4-tri-O-methylellagic acid (2) showed cytotoxicity against L5178Y mouse lymphoma cells with IC50 values of 9.4 and 29.0 μM, respectively.

Introduction

It is well known that many endophytic fungi are capable of generating the same secondary metabolites as their host plants [1] with some notable examples being paclitaxel [2], camptothecin [3], podophyllotoxin [4], or hypericin [5]. In fact, since the bioactive compound paclitaxel (taxol) was discovered from the endophytic fungus Taxomyces andreanae in 1993, scientists have increasingly paid closer attention to relationships between endophytic fungi and their host plants in search for novel and biologically active compounds [6].

In the course of our ongoing research on bioactive natural products from endophytic fungi and their associated host plants [7], [8], [9], [10], we became interested in the African rain forest tree Combretum dolichopetalum Engl. and Diels (Combretaceae), a plant which is hitherto chemically unexplored but is reported to posses hepatoprotective [11], antiulcer [12] and antidiabetic activities [13] and is used traditionally for the treatment of gastrointestinal disorders [14]. Furthermore, in order to examine whether endophytic fungi from C. dolichopetalum were capable of producing the same or similar bioactive compounds as those present in their host plant, endophytic fungi from the plant were explored, resulting in the isolation of Nigrospora oryzae from leaves of C. dolichopetalum.

Herein we report the isolation, structural elucidation of nine compounds including one new natural product 4-dehydroxyaltersolanol A (9) from the endophytic fungus and its host plant as well as their cytotoxicity. Possible biogenetic relationships among some of the isolated compounds are also discussed. To the best of our knowledge, this is the first report of secondary metabolites from C. dolichopetalum and also the first report on endophytic fungi from this plant.

Section snippets

Results and discussion

Our chemical examination of the roots of C. dolichopetalum led to the isolation of six known compounds including ellagic acid (1) [15], 3,3′,4-tri-O-methylellagic acid (2) [16], arjunolic acid (3) [17], 4′-dihydrophaseic acid (4) [18], echinulin (5) [19] and arestrictin B (6) [20]. Investigation of the EtOAc extract of the endophytic fungus N. oryzae yielded the new altersolanol derivative, 4-dehydroxyaltersolanol A (9), in addition to two known sesquiterpenoids, (S)-7′-hydroxyabscisic acid (7)

General experimental procedures

1H and 13C NMR spectra were recorded on Bruker ARX 300 or AVANCE DMX 600 NMR spectrometers. ESI-MS spectra were measured on a Finnigan LCQ-Deca mass spectrometer and HRESI-MS spectra were recorded with a FTHRMS-Orbitrap (Thermo Finnigan) mass spectrometer. Optical rotations were recorded on a Perkin-Elmer-241 MC polarimeter. Solvents were refined before utilization, and spectroscopic-grade solvents were utilized for spectroscopic measurements. HPLC investigation was performed utilizing a HPLC

Acknowledgments

Financial support by a grant from BMBF (16GW0107K) to P. P. is gratefully acknowledged.

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