title: Structure elucidation and antimalarial activity of apicidin F: an apicidin-like compound produced by Fusarium fujikuroi.
abstract: Apicidins are cyclic tetrapeptides with histone deacetylase inhibitory activity. Since their discovery in 1996 a multitude of studies concerning the activity against protozoa and certain cancer cell lines of natural and synthetic apicidin analogues have been published. Until now, the only published natural sources of apicidin are the fungus Fusarium pallidoroseum, later known as F. semitectum and two unspecified Fusarium strains. The biosynthetic origin of apicidins could be associated with a gene cluster, and a biosynthetic pathway has been proposed. Recently, our group was able to identify for the first time an apicidin-like gene cluster in F. fujikuroi that apparently does not lead to the production of any known apicidin analogue. By overexpressing the pathway-specific transcription factor we were able to identify a new apicidin-like compound. The present study provides the complete structure elucidation of the new compound, named apicidin F. Activity evaluation against Plasmodium falciparum showed good in vitro activity with an IC50 value of 0.67 μM.
authors.affiliation: Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster , Corrensstraße 45, 48149 Münster, Germany.
authors.forename: Katharina Walburga
authors.initials: KW
authors.lastname: von Bargen
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Niehaus
authors.forename: Klaus
authors.initials: K
authors.lastname: Bergander
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Bettina
authors.initials: B
authors.lastname: Tudzynski
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005670:Fusarium / Q000737:chemistry*; D056572:Histone Deacetylase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D056572:Histone Deacetylase Inhibitors; D010456:Peptides, Cyclic; C586138:apicidin F; D006655:Histone Deacetylases