CP-84,657, a potent polyether anticoccidial related to portmicin and produced by Actinomadura sp.

Abstract

A new polyether antibiotic CP-84,657 (C45H78O14) was isolated by solvent extraction from the fermentation broth of Actinomadura sp. (ATCC 53708). Following purification by column chromatography and crystallization, the structure of CP-84,657 was elucidated by spectroscopic (NMRand MS) methods. The absolute stereochemistry was determined by a single crystal X-ray analysis of the corresponding rubidium salt. CP-84,657 is among the most potent anticoccidal agents known, effectively controlling the Eimeria species that are the major causative agents of chicken coccidiosis at doses of 5 mg/kg or less in feed. It is also active in vitro against certain Gram-positive bacteria, as well as the spirochete, Treponema hyodysenteriae.Interest in polyether antibiotics has remained at a high level for over 20 years, owing largely to the commercial importance of this class of drugs in veterinary medicine. For example, monensin1*, lasalocid1* and salinomycin2) are marketed as anticoccidial agents for poultry, and are used as growth permittants in cattle or swine. Narasin1* and maduramicin3) are also used as anticoccidial agents.In the process of screening actinomycetes for novel antimicrobial substances, a new strain of Actinomadura sp. was found to produce a new polyether antibiotic, CP-84,657 (1). This compound, which was very potent versus Eimeria coccidia in chickens, was shown to be structurally similar to portmicin4), Upon completion of this work5), studies were presented by Hamill et al.6) on the discovery of a new polyether antibiotic, A82810, produced by Actinomadura fibrosa. Although an X-ray analysis of A82810 has not been reported, based on 13C and *H NMRdata it appears that CP-84,657 and A82810 are identical.The present paper describes the taxonomy and fermentation studies on the producing organism of CP-84,657, as well as the isolation, characterization and biological testing of this antibiotic.

Anticoccidial Efficacy and Chicken Toleration of Potent New Polyether Ionophores.

“…In battery efficacy trials, ionophore CP-84,657 at doses down to 4 ppm was as effective as commercial reference ionophores at preventing coccidiosis-induced lesions and weight suppression. These efficacy data are consistent with initial testing reported previously (Dirlam et al, 1990a) with treatment groups of three to five birds, which demonstrated full efficacy for the ionophore CP-84,657 at 5 ppm. In the present studies, the CP-84,657 ionophore at 4 ppm was well tolerated in chickens up to 49 days in floor pens, giving performance values equal to commercial standards.…”

“…Following completion of the work reported herein, a compound thought to be identical to CP-84,657 was described by an independent group, and was designated by them as A82810 (Hamill et al, 1989). Preliminary evaluation of a third potent ionophore, CP-82,996, has been reported (Dirlam et al, 1990a).…”

Nomimicin, a new spirotetronate-class polyketide from an actinomycete of the genus Actinomadura

“…1 Almost a half of the known microbial bioactive compounds are derived from actinomycetes, and specifically Streptomyces accounts for more than 70% of the actinomycete-derived metabolites. 2 Among the nonStreptomyces species, Micromonospora is the leading producer of secondary metabolites, including polyketides, peptides and glycosides, whereas Actinomadura is known as a producer of chemically and biologically unique polyketides such as antitumor enediynes, 3 mannose-binding quinone glycosides with antifungal and anti-HIV activities 4 and anticoccidial polyethers, 5 accounting for up to 350 compounds reported as of 2005. 2 During our continuing investigation on the metabolites from actinomycetes of nonStreptomyces group, 6,7 a new spirotetronate antibiotic of polyketide origin, nomimicin (1, Figure 1), was isolated from the culture extract of Actinomadura sp.…”

Astonishing diversity of natural surfactants: 2. Polyether glycosidic ionophores and macrocyclic glycosides

“…Polyether 39 is among the most potent anticoccidial agents known, effectively controlling the major Eimeria species (E. tenella, E. acervulina, E. maxima, and E. necatrix) responsible for avian coccidiosis at doses of 5 mg/kg or less in feed. This compound is also active against certain Gram-positive bacteria in vitro as well as the spirochete S. hyodysenteriae, the causative agent in swine dysentery (94,95). The ionophores W341C 40 and CP-120509 41 (96) were produced by Streptomyces W341 (57).…”