ABSTRACT
Five diastereomeric polyketide glycosides, roselipins 3A-3E (1-5), have been isolated from the acetone extract of Clonostachys candelabrum on the basis of their positive anthelmintic activity. The structures of these compounds were elucidated by comparison of their NMR and MS data to those of previously reported roselipins and related structures, and were confirmed by 2D-NMR spectral analysis. Known compounds linoleic acid (6) and aurantiogliocladin (7) were also isolated as active anthelmintic components, although much less potent than the roselipins.
Subject(s)
Anthelmintics/chemistry , Anthelmintics/pharmacology , Hypocreales/chemistry , Animals , Biological Assay , Cecum/parasitology , Chromatography, High Pressure Liquid , Indicators and Reagents , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Nematode Infections/drug therapy , Nematode Infections/parasitology , Nematospiroides dubius/drug effects , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, Ultraviolet , Stomach/parasitology , Structure-Activity RelationshipABSTRACT
Noreupenifeldin ( 2), a new monotropolone derivative of the bistropolone eupenifeldin ( 1), was isolated from an unidentified ascomycete by bioassay-guided fractionation as part of our search for new anthelmintics. The structure of 1 was confirmed by comparison with literature data. The structure of 2 was elucidated from MS and 1D and 2D NMR data. Compounds 1 and 2 are diastereomers of pycnidione ( 3) and epolone A ( 4), respectively. Compounds 1- 3 were evaluated for their anthelmintic activity against the parasitic worm Hemonchus contortus. Compounds 1 and 3 exhibited modest in vitro activity, showing EC 90 50 and 83 microg/mL, respectively, in reducing motility of L3 larvae of H. contortus. Compound 2 was inactive, indicating that the second tropolone moiety is required for activity.
Subject(s)
Ascomycota/chemistry , Tropolone/analogs & derivatives , Tropolone/isolation & purification , Animals , Haemonchus/drug effects , Molecular Structure , Tropolone/chemistry , Tropolone/pharmacologyABSTRACT
Parasitic diseases caused by helminthes lead to significant health hazards to animals resulting in enormous economic impact. While a number of anthelmintics are currently available, all are encountering resistance and ones with a mode of action are needed. We report herein bioassay-guided isolation of three anthelmintic flavones 1-3, including the flavone, 5,6,2',5',6'-pentamethoxy-3',4'-methylenedioxyflavone (3) from the methanol extract of Struthiola argentea (Thymelaeaceae). The structure of 3 was elucidated by analysis of its 1D and 2D NMR and MS data. The two major flavones produced by this plant were also isolated and identified as yuankanin (4) and amentoflavone (5). A number of flavones related to the compounds isolated from S. argentea were acquired and tested to ascertain structure activity relationships. The isolation, structure, anthelmintic activity and structure activity relationships of the flavones are described. Compound 3 exhibited the most potent in vitro activity with 90% inhibition of larval motility at 3.1 microg/mL and compound 15 showed modest in vivo activity.
