In vitro microbiological characterization of novel cyclic homopentapeptides, CP-101,680 and CP-163,234, for animal health use.
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.
Norcia
L J
LJ
Central Research Division, Pfizer Inc., Groton, CT 06340, USA.
Silvia
A M
AM
Dirlam
J P
JP
Schnur
R C
RC
Bergeron
J M
JM
Retsema
J A
JA
Hayashi
S F
SF
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
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