Original Article

Anthelmintic Macrolactams from Nonomuraea turkmeniaca MA7381

Sloan Ayers, Deborah L. Zink, Joanne Staats Powell, Christine M. Brown, Alan Grund, Olga Genilloud, Oscar Salazar, Donald Thompson, Sheo B. Singh

Received: November 16, 2007 / Accepted: January 18, 2008
© Japan Antibiotics Research Association

Abstract 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. 1~3 exhibited in vitro activity (EC90 <1.0~1.7 μg/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.

Keywords macrocyclic lactone, fluvirucins, anthelmintic, Nonomuraea species, Natural product isolation and structure elucidation

S. B. Singh (Corresponding author), S. Ayers, D. L. Zink: Natural Products Chemistry, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, E-mail: sheo_singh@merck.com
J. S. Powell, C. M. Brown, D. Thompson: Merck and Co., Inc., Branchburg Farm, 203 River Road, Somerville, NJ 08876
A. Grund: Bio-Technical Resources, 1035 South 7th St., Manitowoc, WI 54220
O. Genilloud, O. Salazar: Centro de Investigación Básica, Merck, Sharp & Dohme de Espana, S.A., Josefa Valcarcel 38, 28027 Madrid, Spain