TY - JOUR
T1 - In Vitro And In Vivo Characterization Of Novel 8-Methoxy Derivatives Of Chlortetracycline
AU - Cacciapuoti, A.
AU - Moss, E. L.
AU - Menzel, F.
AU - Cramer, C. Adam
AU - Weiss, W.
AU - Loebenberg, D.
AU - Loebenberg, Hare
AU - Miller, G. H.
PY - 1987
Y1 - 1987
N2 - The in vitro activities of three new 8-methoxychlortetracyclines, Sch 36969, 33256 and 34164 were compared to tetracycline, minocycline and doxycycline. Against aerobic Gram-negative rods Sch 36969 had a geometric mean MIC (GMM) of 4.2 μg/ml, about 8-fold more potent than Sch 33256, and similar to all the other compounds. Sch 36969 also had good activity against methicillin-resistant (GMM, 0.21 μg/ml) and -susceptible Staphylococci (GMM, 0.14 μg/ml), Streptococci (GMM, 0.06 μg/ml), and most anaerobic bacteria (GMM, <0.5 μg/ml). In general, Sch 36969 was similar to, or more potent than, all the other com-pounds tested. Serum levels of Sch 36969 in squirrel monkeys were 4-fold lower (AUC, 4.5 hours/ml) than those of chlortetracycline (AUC, 16.1 μg·hours/ml). In mouse pro-tection tests (PD50s) against various strains of bacteria, Sch 36969 was similar in activity to tetracycline, but up to 6-fold less active than chlortetracycline. The structure activity rela-tionships for these new chlortetracyclines are described.
AB - The in vitro activities of three new 8-methoxychlortetracyclines, Sch 36969, 33256 and 34164 were compared to tetracycline, minocycline and doxycycline. Against aerobic Gram-negative rods Sch 36969 had a geometric mean MIC (GMM) of 4.2 μg/ml, about 8-fold more potent than Sch 33256, and similar to all the other compounds. Sch 36969 also had good activity against methicillin-resistant (GMM, 0.21 μg/ml) and -susceptible Staphylococci (GMM, 0.14 μg/ml), Streptococci (GMM, 0.06 μg/ml), and most anaerobic bacteria (GMM, <0.5 μg/ml). In general, Sch 36969 was similar to, or more potent than, all the other com-pounds tested. Serum levels of Sch 36969 in squirrel monkeys were 4-fold lower (AUC, 4.5 hours/ml) than those of chlortetracycline (AUC, 16.1 μg·hours/ml). In mouse pro-tection tests (PD50s) against various strains of bacteria, Sch 36969 was similar in activity to tetracycline, but up to 6-fold less active than chlortetracycline. The structure activity rela-tionships for these new chlortetracyclines are described.
UR - http://www.scopus.com/inward/record.url?scp=0023635803&partnerID=8YFLogxK
U2 - 10.7164/antibiotics.40.1426
DO - 10.7164/antibiotics.40.1426
M3 - Article
C2 - 3680008
AN - SCOPUS:0023635803
SN - 0021-8820
VL - 40
SP - 1426
EP - 1430
JO - Journal of Antibiotics
JF - Journal of Antibiotics
IS - 10
ER -