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Title: 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

Author
item KASANAH, NOER - UNIVERSITY OF MISSISSIPPI
item LUCAS-FARR, LORELEI - University Of Mississippi
item GHOLIPOUR, ABBAS - University Of Mississippi
item Wedge, David
item HAMANN, MARK - University Of Mississippi

Submitted to: Marine Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/14/2013
Publication Date: 2/20/2014
Citation: Kasanah, N., Lucas-Farr, L., Gholipour, A., Wedge, D.E., Hamann, M.T. 2014. 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. Marine Biotechnology. 16:412-422.

Interpretive Summary: Manzamines are a group of sponge-derived alkaloids characterized as a complex heterocyclic ring system bearing a B-carboline moiety. To date there are 16 species belonging to 8 families of sponges that have been confirmed to yield the B-carboline containing manzamine and manzamine-related alkaloids. In this paper we report the metabolism of manzamine as one possible mechanism of inherent resistance of Fusarium spp. to this class of alkaloids. In addition, we discuss the impact of resistance and modification of structure of manzamine alkaloids. The manzamine alkaloids isolated from sponge Acanthrostrongylophora sp. were evaluated for in vitro antifungal activity against the phytopathogenic strains of F. solani, F. oxysporum and F. proliferatum.

Technical Abstract: As a part of our continuing investigation of the manzamine alkaloids we studied the in vitro activity of the ß-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.