In vitro and in vivo evaluation of C-20- and C-23-modified derivatives of tylosin against veterinary pathogens.
Three series of semi-synthetic derivatives of tylosin-related macrolides were evaluated for utility in veterinary medicine. 23-Modified derivatives of 5-O-mycaminosyltylonolide (OMT) possessed potent activity in vitro against species of Pasteurella and Mycoplasma. An experimental infection in chicks caused by Pasteurella multocida was utilized to evaluate efficacy; several of these derivatives of OMT effectively treated the infection when given subcutaneously, but none were effective after oral administration in drinking water. Macrolides retaining the 4'-O-mycarosyl moiety (tylosin, DMT) had relatively poor activity against Pasteurella in vitro. Certain 20-modified derivatives of desmycosin demonstrated good oral bioavailability in chicks and a lead compound with oral efficacy in the Pasteurella infection model was discovered.
Kirst
H A
HA
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Ose
E E
EE
Toth
J E
JE
Willard
K E
KE
Debono
M
M
Felty-Duckworth
A M
AM
Pekarek
R S
RS
D000818:Animals; D007933:Leucomycins / Q000494:pharmacology*; D051379:Mice; D009174:Mycoplasma / Q000187:drug effects*; D010325:Pasteurella / Q000187:drug effects*; D010326:Pasteurella Infections / Q000188:drug therapy; D013329:Structure-Activity Relationship; D015645:Tylosin / Q000031:analogs & derivatives
D007933:Leucomycins; C052318:tylosin B; D015645:Tylosin