Anthelmintic macrolactams from Nonomuraea turkmeniaca MA7364.
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.
Ayers
Sloan
S
Natural Products Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA.
Zink
Deborah L
DL
Mohn
Kenneth
K
Powell
Joanne Staats
JS
Brown
Christine M
CM
Murphy
Terry
T
Grund
Alan
A
Genilloud
Olga
O
Salazar
Oscar
O
Thompson
Donald
D
Singh
Sheo B
SB
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*
C523228:6-desmethyl-N-methylfluvirucin A1; D000871:Anthelmintics; D007769:Lactams; C523229:N-methylfluvirucin A1