Metabolomics-Guided Isolation of Anti-Trypanosomal Compounds from Endophytic Fungi of the Mangrove plant Avicennia Lanata

(E-pub Ahead of Print)

Author(s): Noor Wini Mazlan*, Rothwelle Tate, Yusnaini Md. Yusoff, Carol Clements, RuAngelie Edrada-Ebel.

Journal Name: Current Medicinal Chemistry

Abstract:

Endophytic fungi have been explored not just for their ecological functions but also for their secondary metabolites as a new source of these pharmacologically active natural products. Accordingly, many structurally unique and biologically active compounds have been obtained from the cultures of endophytic fungi. Fusarium sp. and Lasiodiplodia theobromae were isolated from the root and stem of the mangrove plant Avicennia lanata, respectively, collected from Terengganu, Malaysia. High-resolution mass spectrometry and NMR spectroscopy were used as metabolomics profiling tools to identify and optimize the production of bioactive secondary metabolites in both strains at different growth stages and culture media. The spectral data was processed by utilizing a quantitative expression analysis software, the modified Mzmine 2.10, an in house MS-Excel macro coupled with Antimarin (Antibase and Marinlit) and Dictionary of Natural Products databases for dereplication studies. The investigation for the potential bioactive metabolites from a 15-day rice culture of Fusarium sp. yielded four 1,4-naphthoquinone with naphthazarin structures (1-4). On the other hand, the endophytic fungus L. theobromae grown on the 15-day solid rice culture produced dihydroisocoumarins (5 to 8). All the isolated compounds (1 to 8) showed significant activity against Trypanosoma brucei brucei with MIC values of 0.32-12.5 μM. Preliminary cytotoxicity screening against normal prostate cells (PNT2A) was also performed. All compounds exhibited low cytotoxicity, with compounds 3 and 4 showing the lowest cytotoxicity of only 22.3% and 38.6% of the control values at 100 μg/mL, respectively. Structure elucidation of the isolated secondary metabolites was achieved using 2D-NMR and HRESI-MS as well as comparison with literature data.

Keywords: Endophytic fungi, dereplication, metabolomics, mass spectrometry, multivariate analysis

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/0929867326666190704130105
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