ABSTRACT
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.
Subject(s)
Anthelmintics/chemistry , Anthelmintics/pharmacology , Flavones/chemistry , Flavones/pharmacology , Thymelaeaceae/chemistry , Animals , Haemonchus/drug effects , Magnetic Resonance Spectroscopy , Mice , Molecular StructureABSTRACT
Haemonchus contortus is a worm that causes serious infections in livestock. Two new perylenequinones, scutiaquinone A (1) and scutiaquinone B (2), have been isolated from a methanol extract of the roots of Scutia myrtina by bioassay-guided fractionation, using an assay that kills this parasite in vitro. The structures of compounds 1 and 2 were elucidated by analysis of their 1D- and 2D-NMR and MS spectra. The isolation, structure, and anthelmintic activities of compounds 1 and 2 are reported.
Subject(s)
Animals, Domestic/parasitology , Anthelmintics , Haemonchus/drug effects , Perylene/analogs & derivatives , Plants, Medicinal/chemistry , Quinones , Rhamnaceae/chemistry , Animals , Anthelmintics/chemistry , Anthelmintics/isolation & purification , Anthelmintics/pharmacology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Perylene/chemistry , Perylene/isolation & purification , Perylene/pharmacology , Plant Roots/chemistry , Quinones/chemistry , Quinones/isolation & purification , Quinones/pharmacology , South AfricaABSTRACT
Two known aporphine alkaloids, (S)-dicentrine (1) and (S)-neolitsine (2), have been isolated from the MeOH extract of the aerial parts of Cissampelos capensis (Menispermaceae). The structures of these compounds were elucidated by NMR and MS analysis and comparison to literature data. These compounds were isolated by bioassay-guided fractionation using the Haemonchus contortus larval development assay. Compounds 1 and 2 exhibited EC90 values (concentration at which 90% loss of larval motility is observed) of 6.3 and 6.4 microg/mL, respectively. In an IN VIVO assay, administration of 1 resulted in 67% reduction of worm counts in mice at 25 mg/kg when dosed orally.
