title: Chemical and bioactive natural products from Microthyriaceae sp., an endophytic fungus from a tropical grass.
abstract: In screening for natural products with antiparasitic activity, an endophytic fungus, strain F2611, isolated from above-ground tissue of the tropical grass Paspalum conjugatum (Poaceae) in Panama, was chosen for bioactive principle elucidation. Cultivation on malt extract agar (MEA) followed by bioassay-guided chromatographic fractionation of the extract led to the isolation of the new polyketide integrasone B (1) and two known mycotoxins, sterigmatocystin (2) and secosterigmatocystin (3). Sterigmatocystin (2) was found to be the main antiparasitic compound in the fermentation extract of this fungus, possessing potent and selective antiparasitic activity against Trypanosoma cruzi, the cause of Chagas disease, with an IC50 value of 0.13 μmol l(-1) . Compounds 2 and 3 showed high cytotoxicity against Vero cells (IC50 of 0.06 and 0.97 μmol l(-1) , respectively). The new natural product integrasone B (1), which was co-purified from the active fractions, constitutes the second report of a natural product possessing an epoxyquinone with a lactone ring and exhibited no significant biological activity. Strain F2611 represents a previously undescribed taxon within the Microthyriaceae (Dothideomycetes, Ascomycota).
  
  
  CONCLUSIONS
  The present study attributes new antiparasitic and psychoactive biological activities to sterigmatocystin (2), and describes the structure elucidation of the new natural product integrasone B (1), which possesses a rare epoxyquinone with a lactone ring moiety. This is also the first report of sterigmatocystin (2) isolation in a fungal strain from this family, broadening the taxonomic range of sterigmatocystin-producing fungi. The study also presents taxonomic analyses indicating that strain F2611 is strongly supported as a member of the Microthyriaceae (Ascomycota), but is not a member of any previously known or sequenced genus.
authors.affiliation: Laboratory of Tropical Bioorganic Chemistry, Faculty of Natural Exact Sciences and Technology, University of Panama, Panama City, Republic of Panama; Smithsonian Tropical Research Institute, Balboa, Panama City, Republic of Panama; Centro de Biodiversidade, Genómica Integrativa e Funcional (BioFIG), Universidade de Lisboa, Faculdade de Ciências, Edifício ICAT/TecLabs, Campus da FCUL, Campo Grande, Lisboa, Portugal.
authors.forename: C
authors.initials: C
authors.lastname: Almeida
authors.forename: H
authors.initials: H
authors.lastname: Ortega
authors.forename: S
authors.initials: S
authors.lastname: Higginbotham
authors.forename: C
authors.initials: C
authors.lastname: Spadafora
authors.forename: A E
authors.initials: AE
authors.lastname: Arnold
authors.forename: P D
authors.initials: PD
authors.lastname: Coley
authors.forename: T A
authors.initials: TA
authors.lastname: Kursar
authors.forename: W H
authors.initials: WH
authors.lastname: Gerwick
authors.forename: L
authors.initials: L
authors.lastname: Cubilla-Rios
mesh_terms: D000818:Animals; D001203:Ascomycota / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004271:DNA, Fungal / Q000235:genetics; D021903:DNA, Ribosomal Spacer / Q000235:genetics; D060026:Endophytes / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D058889:Molecular Typing; D016533:Mycological Typing Techniques; D006109:Poaceae / Q000382:microbiology; D061065:Polyketides / Q000302:isolation & purification / Q000494:pharmacology*; D013241:Sterigmatocystin / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects; D014709:Vero Cells
chemical_list: D004271:DNA, Fungal; D021903:DNA, Ribosomal Spacer; D061065:Polyketides; D014344:Trypanocidal Agents; C000592839:integrasone B; D013241:Sterigmatocystin; C000592840:secosterigmatocystin
keywords: antiparasitic activity; endophytic fungi; integrasone B; sterigmatocystin