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Metabolism and Resistance of Fusarium spp. to the Manzamine Alkaloids via a Putative Retro Pictet-Spengler Reaction and Utility of the Rational Design of Antimalarial and Antifungal Agents

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Abstract

As a part of our continuing investigation of the manzamine alkaloids we studied the in vitro activity of the β-carboline containing manzamine alkaloids against Fusarium solani, Fusarium oxysporium, and Fusarium proliferatum by employing several bioassay techniques including one-dimensional direct bioautography, dilution, and plate susceptibility, and microtiter broth assays. In addition, we also studied the metabolism of the manzamine alkaloids by Fusarium spp. in order to facilitate the redesign of the compounds to prevent resistance of Fusarium spp. through metabolism. The present research reveals that the manzamine alkaloids are inactive against Fusarium spp. and the fungi transform manzamines via hydrolysis, reduction, and a retro Pictet-Spengler reaction. This is the first report to demonstrate an enzymatically retro Pictet-Spengler reaction. The results of this study reveal the utility of the rational design of metabolically stable antifungal agents from this class and the development of manzamine alkaloids as antimalarial drugs through the utilization of Fusarium’s metabolic products to reconstruct the molecule.

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Authors and Affiliations

  1. Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, Oxford, MS, USA

    Noer Kasanah, Lorelei Lucas Farr, Abbas Gholipour & Mark T. Hamann

  2. Natural Product Utility-USDA-ARS-NPURU, The University of Mississippi, Oxford, MS, USA

    David E. Wedge

  3. Department of Fisheries, Faculty of Agriculture, Gadjah Mada University, Yogyakarta, Indonesia

    Noer Kasanah

Authors
  1. Noer Kasanah
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  2. Lorelei Lucas Farr
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  3. Abbas Gholipour
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  4. David E. Wedge
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  5. Mark T. Hamann
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Correspondence to Noer Kasanah.

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Kasanah, N., Farr, L.L., Gholipour, A. et al. Metabolism and Resistance of Fusarium spp. to the Manzamine Alkaloids via a Putative Retro Pictet-Spengler Reaction and Utility of the Rational Design of Antimalarial and Antifungal Agents. Mar Biotechnol 16, 412–422 (2014). https://doi.org/10.1007/s10126-014-9557-0

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  • DOI: https://doi.org/10.1007/s10126-014-9557-0

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