Title:Metabolomics-Guided Isolation of Anti-Trypanosomal Compounds from Endophytic Fungi of the Mangrove plant <i>Avicennia Lanata</i>
VOLUME: 27 ISSUE: 11
Author(s):Noor Wini Mazlan*, Rothwelle Tate, Yusnaini Md. Yusoff, Carol Clements and RuAngelie Edrada-Ebel*
Affiliation:Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, Scotland, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, Scotland, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, Scotland, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, Scotland, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, The John Arbuthnott Building, 161 Cathedral Street, Glasgow G4 0RE, Scotland
Keywords:Endophytic fungi, dereplication, metabolomics, mass spectrometry, multivariate analysis, secondary
metabolites.
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
Mzmine 2, a quantitative expression analysis software and an in house MS-Excel macro coupled
with the 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 (5-8). All the
isolated compounds (1-8) 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.
