Synthetic modification of a novel microbial ionophore: exploration of anticoccidial structure-activity relationships.
While fermentation-derived polyether ionophores such as salinomycin are the dominant class of anticoccidial feed additives, there is little information concerning the structural features which confer optimal potency/efficacy in this important series. The recently discovered microbial polyether 1a, featuring potent, broad-spectrum anticoccidial activity, was employed as a template to explore structure-activity relationships. A number of single-step synthetic modifications targeted structural changes in both the lipophilic carbon backbone and the ion-binding cavity of 1a. Although previous semisynthetic transformations among the polyether ionophores almost always resulted in a substantial loss of anticoccidial activity, we obtained several analogues, altered on the periphery of the ionophore-ion complex, which retain good potency and efficacy. Monoglycone 7 (semduramicin sodium) has the most impressive anticoccidial profile of this series, and is undergoing further biological testing under field conditions.
Glazer
E A
EA
Central Research Division, Pfizer Inc, Groton, Connecticut 06340.
Koss
D A
DA
Olson
J A
JA
Ricketts
A P
AP
Schaaf
T K
TK
Wiscount
R J
RJ
D000818:Animals; D002645:Chickens; D003049:Coccidiostats / Q000737:chemistry* / Q000494:pharmacology; D016786:Eimeria tenella / Q000187:drug effects; D007476:Ionophores / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D003049:Coccidiostats; D007476:Ionophores