Anthelmintic macrolactams from Nonomuraea turkmeniaca MA7381.
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.
Ayers
Sloan
S
Natural Products Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. sheo_singh@merck.com
Zink
Deborah L
DL
Powell
Joanne Staats
JS
Brown
Christine M
CM
Grund
Alan
A
Genilloud
Olga
O
Salazar
Oscar
O
Thompson
Donald
D
Singh
Sheo B
SB
D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D007769:Lactams / Q000737:chemistry / Q000302:isolation & purification* / Q000627:therapeutic use; D051379:Mice; D009351:Nematospiroides dubius / Q000187:drug effects; D017206:Strongylida Infections / Q000188:drug therapy
D000871:Anthelmintics; D007769:Lactams; D007559:Ivermectin; C019264:avermectin