title: In vitro microbiological characterization of novel cyclic homopentapeptides, CP-101,680 and CP-163,234, for animal health use.
abstract: Two cyclic homopentapeptides, CP-101,680 and CP-163,234 [6a-(3',4'-dichlorophenylamino) analogs of viomycin and capreomycin, respectively], were identified as novel antibacterial agents for the treatment of animal disease, especially for livestock respiratory disease. The in vitro microbiological characterization of both CP-101,680 and CP-163,234 was carried out using their parent compounds, viomycin and capreomycin, as controls. This characterization included antibacterial spectrum, influence of media, inoculum size, pH, EDTA, polymixin B nonapeptide (PMBN), serum, cell-free protein synthesis inhibition, and time-kill kinetics. Our results indicated that the capreomycin analog, CP-163,234, showed slightly improved in vitro potency over the viomycin analog, CP-101,680. Both analogs showed very potent cell-free protein synthesis inhibition activity and were bactericidal against Pasteurella haemolytica, P. multocida and Actinobacillus pleuropneumoniae at the level of 4 times and 8 times MICs. CP-163,234 was bactericidal at the level of 4x and 8x MIC against E. coli, but re-growth was observed after 24 hours incubation at both concentrations of CP-101,680.
authors.affiliation: Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Norcia
authors.forename: A M
authors.initials: AM
authors.lastname: Silvia
authors.forename: J P
authors.initials: JP
authors.lastname: Dirlam
authors.forename: R C
authors.initials: RC
authors.lastname: Schnur
authors.forename: J M
authors.initials: JM
authors.lastname: Bergeron
authors.forename: J A
authors.initials: JA
authors.lastname: Retsema
authors.forename: S F
authors.initials: SF
authors.lastname: Hayashi
mesh_terms: D000820:Animal Diseases / Q000188:drug therapy*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D002207:Capreomycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003470:Culture Media; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D011112:Polymyxin B / Q000031:analogs & derivatives / Q000494:pharmacology; D014756:Viomycin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C403872:CP 101680; C403873:CP 163234; D003470:Culture Media; D002207:Capreomycin; C038934:polymyxin B nonapeptide; D004492:Edetic Acid; D011112:Polymyxin B; D014756:Viomycin