RESUMO
A new macrolactam, fluvirucin B0 (1), and two known macrolactams, Sch 38516/fluvirucin B1 (2) and Sch 39185/fluvirucin B3 (3), have been isolated from an acetone extract of a strain of Nonomuraea turkmeniaca. These compounds were isolated by bioassay-guided fractionation as part of our search for new anthelmintics. The structures of these compounds were elucidated by comparison of their NMR and MS data to those of previously reported fluvirucins, and confirmed by 2D-NMR. 1approximately 3 exhibited in vitro activity (EC90 <1.0 approximately 1.7 microg/ml) against Haemonchus contortus larvae, but were ineffective in reducing worm counts in vivo against Heligmosomoides polygyrus in mice at 50 mg/kg dosed intramuscularly.
Assuntos
Anti-Helmínticos/isolamento & purificação , Ivermectina/análogos & derivados , Lactamas/isolamento & purificação , Animais , Anti-Helmínticos/química , Anti-Helmínticos/uso terapêutico , Ivermectina/química , Ivermectina/isolamento & purificação , Ivermectina/uso terapêutico , Lactamas/química , Lactamas/uso terapêutico , Camundongos , Nematospiroides dubius/efeitos dos fármacos , Infecções por Strongylida/tratamento farmacológicoRESUMO
Two new macrolactams, 6-desmethyl-N-methylfluvirucin A1 (1) and N-methylfluvirucin A1 (2), have been isolated from the acetone extract of Nonomuraea turkmeniaca MA7364. These compounds were isolated by bioassay-guided fractionation as part of our search for new anthelmintics. The structures of these compounds were elucidated by comparison of their NMR and MS data to those of previously reported fluvirucins and confirmed by 2D NMR. Compound 1 exhibited in vitro activity (EC(90) 15 +/- 5 microg/mL) against Haemonchus contortus larvae, whereas compound 2, while a bit less active in vitro (EC(90) 29 +/- 8 microg/mL), showed modest in vivo activity against a surrogate organism, Heligmosomoides polygyrus in mice, at 50 mg/kg.
Assuntos
Actinomycetales/química , Anti-Helmínticos , Haemonchus/efeitos dos fármacos , Lactamas , Plantas Medicinais/química , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Lactamas/química , Lactamas/isolamento & purificação , Lactamas/farmacologia , Larva/efeitos dos fármacos , México , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear BiomolecularRESUMO
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.
Assuntos
Animais Domésticos/parasitologia , Anti-Helmínticos , Haemonchus/efeitos dos fármacos , Perileno/análogos & derivados , Plantas Medicinais/química , Quinonas , Rhamnaceae/química , Animais , Anti-Helmínticos/química , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Perileno/química , Perileno/isolamento & purificação , Perileno/farmacologia , Raízes de Plantas/química , Quinonas/química , Quinonas/isolamento & purificação , Quinonas/farmacologia , África do SulRESUMO
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.