Pochonins A-F, new antiviral and antiparasitic resorcylic acid lactones from Pochonia chlamydosporia var. catenulata.
Monorden (1) and the novel resorcylic acid lactones pochonins A (2), B (4), C (6), D (7), and E (8) as well as tetrahydromonorden (5) and pseurotin A (22) were isolated from cultures of the clavicipitaceous hyphomycete Pochonia chlamydosporia var. catenulata strain P 0297. Fermentation of P 0297 in bromide-containing culture media led to a shift in secondary metabolite production and yielded monocillins III (3) and II (9) as major metabolites besides monorden (1) as well as the novel compounds pochonin F (10) and a monocillin II glycoside (11) as minor metabolites. Most of these compounds showed moderate activities in a cellular replication assay against Herpes Simplex Virus 1 (HSV1) and against the parasitic protozoan Eimeria tenella. In contrast to the structurally related zearalenone derivatives none of the metabolites of strain P 0297 were found to be active in a fluorescence polarization assay for determination of modulatory activities on the human estrogenic receptor ERbeta. Beta-zearalenol (17), but not zearalenone (15) and alpha-zearalenol (16), showed antiherpetic effects. We report the production, isolation, and structure elucidation of compounds 1-11 and their biological characterization.
Hellwig
Veronika
V
Bayer Health Care, Pharma Research, Life Science Center Natural Products, P.O. Box 101709, D-42096 Wuppertal, Germany. Veronika.Hellwig.VH@bayer-ag-de
Mayer-Bartschmid
Anke
A
Müller
Hartwig
H
Greif
Gisela
G
Kleymann
Gerald
G
Zitzmann
Werner
W
Tichy
Hans-Volker
HV
Stadler
Marc
M
D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D016786:Eimeria tenella / Q000187:drug effects; D005858:Germany; D018259:Herpesvirus 1, Human / Q000187:drug effects; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D018942:Macrolides; D008855:Microscopy, Electron, Scanning; D003904:Mitosporic Fungi / Q000737:chemistry* / Q000648:ultrastructure; D015394:Molecular Structure; D009491:Neurospora / Q000187:drug effects; D013237:Stereoisomerism
D000981:Antiprotozoal Agents; D000998:Antiviral Agents; D007783:Lactones; D018942:Macrolides; C035359:monorden