title: Chemical constituents of the new endophytic fungus Mycosphaerella sp. nov. and their anti-parasitic activity.
abstract: Chemical investigation of a new endophytic fungus, Mycosphaerella sp. nov. strain F2140, associated with the foliage of the plant Psychotria horizontalis (Rubiaceae) in Panama, resulted in the isolation of cercosporin (1) and a new cercosporin analog (3) as the major components. The structures of minor compounds in the extract were elucidated by detailed spectroscopic analysis as 2-(2-butyl)-6-ethyl-3-hydroxy-6-methylcyclohex-2-ene-1,5-dione (4), 3-(2-butyl)-6-ethyl-5-hydroxy-2-methoxy-6-methyl-cyclohex-2-enone (5), and an isomer of 5 (6). To study the influence of the hydroxy groups on the anti-parasitic activity of cercosporin, compound 1 was acetylated to obtain derivative 2. The isolated compounds 1- 6 were tested in vitro to determine their anti-parasitic activity against the causal agents of malaria (Plasmodium falciparum), leishmaniasis (Leishmania donovani), and Chagas disease (Trypanosoma cruzi). Cytotoxicity and potential anticancer activity of these compounds were evaluated using mammalian Vero cells and MCF7 cancer cell lines, respectively. Compounds 1 and 2 displayed high potency against L. donovani (IC50 0.46 and 0.64 microM), T. cruzi (IC50 1.08 and 0.78 microM), P. falciparum (IC50 1.03 and 2.99 microM), and MCF7 cancer cell lines (IC50 4.68 and 3.56 microM). Compounds 3-6 were not active in these assays at a concentration of 10 microg/mL.
authors.affiliation: Laboratory of Tropical Bioorganic Chemistry, Faculty of Natural Exact Sciences and Technology, University of Panama, Republic of Panama.
authors.forename: Eufemio
authors.initials: E
authors.lastname: Moreno
authors.forename: Titto
authors.initials: T
authors.lastname: Varughese
authors.forename: Carmenza
authors.initials: C
authors.lastname: Spadafora
authors.forename: A Elizabeth
authors.initials: AE
authors.lastname: Arnold
authors.forename: Phyllis D
authors.initials: PD
authors.lastname: Coley
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kursar
authors.forename: William H
authors.initials: WH
authors.lastname: Gerwick
authors.forename: Luis
authors.initials: L
authors.lastname: Cubilla-Rios
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology*; D001203:Ascomycota / Q000737:chemistry*; D002522:Chlorocebus aethiops; D007893:Leishmania donovani / Q000187:drug effects; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry* / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D014349:Trypanosoma cruzi / Q000187:drug effects; D014709:Vero Cells
chemical_list: D000981:Antiprotozoal Agents; D010936:Plant Extracts