The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
ANTHELMINTIC ACTIVITY OF DIOXAPYRROLOMYCIN
GEORGE A. CONDERRAYMOND J. ZIELINSKISANDRA S. JOHNSONMING-SHANG T. KUODEBBIE L. COXVINCENT P. MARSHALLCHRISTOPHER L. HABERPETER J. DIROMASTEPHEN J. NELSONRICHARD D. CONKLINB. LAMAR LEETIMOTHY G. GEARYJ. T. ROTHWELLN. C. SANGSTER
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1992 Volume 45 Issue 6 Pages 977-983

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Abstract

Dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 produced by UC 11065 were evaluated as anthelmintics. Assays used to examine these compounds included effects on the free-living nematode Caenorhabditis elegans, ability to clear target nematodes (Haemonchus contortus and Trichostrongylus colubriformis) from jirds, and clearance of Haemonchus contortus from lambs. A crude extract of UC 11065 containing dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 was active against C. elegans and against H. contortus in the jird. Purified and/or synthetic samples of dioxapyrrolomycin, pyrrolomycin C, pyrrolomycin D, and piericidin C2 were tested in the jird model; only dioxapyrrolomycin exhibited appreciable activity against H. contortus ( ≥ 90.9% clearance at 0.33 mg/jird), while none of the compounds showed appreciable activity against T. colubriformis. Dioxapyrrolomycin cleared 99.9% of H. contortus from lambs at 12.5 mg/kg. An in vitro migration study using susceptible and closantel-resistant H. contortus showed there is cross-resistance between dioxapyrrolomycin and closantel. Dioxapyrrolomycin appears to be a narrow-spectrum anthelmintic which works through a closantel-like mode-of-action.

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