title: Anthelmintic macrolactams from Nonomuraea turkmeniaca MA7364.
abstract: 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.
authors.affiliation: Natural Products Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
authors.forename: Sloan
authors.initials: S
authors.lastname: Ayers
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: Kenneth
authors.initials: K
authors.lastname: Mohn
authors.forename: Joanne Staats
authors.initials: JS
authors.lastname: Powell
authors.forename: Christine M
authors.initials: CM
authors.lastname: Brown
authors.forename: Terry
authors.initials: T
authors.lastname: Murphy
authors.forename: Alan
authors.initials: A
authors.lastname: Grund
authors.forename: Olga
authors.initials: O
authors.lastname: Genilloud
authors.forename: Oscar
authors.initials: O
authors.lastname: Salazar
authors.forename: Donald
authors.initials: D
authors.lastname: Thompson
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000192:Actinomycetales / Q000737:chemistry*; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006189:Haemonchus / Q000187:drug effects*; D007769:Lactams / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D007814:Larva / Q000187:drug effects; D008800:Mexico; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: C523228:6-desmethyl-N-methylfluvirucin A1; D000871:Anthelmintics; D007769:Lactams; C523229:N-methylfluvirucin A1