TY - JOUR
T1 - Antimicrobial and cancer cell growth inhibitory activities of 3β- acetoxy-17β-(L-prolyl)amino-5α-androstane in vitro
AU - Pettit, Robin
AU - Cage, Gary D.
AU - Pettit, George
AU - Liebman, Jessica A.
N1 - Funding Information:
This research was supported by the Arizona Disease Control Research Commission. We thank Dr J. Schmidt, Dr J. Chapuis and L. Williams for cell line data, and Dr F. Hogan for preparing Fig. 1 .
Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2000/8
Y1 - 2000/8
N2 - The in vitro activity of the steroidal amide 3β-acetoxy-17β-(L- prolyl)amino-5α-androstane against 179 Gram-positive clinical isolates was examined. The minimum bactericidal concentration (MBC)/MIC ratios were ≤ 2 for 73% of methicillin-resistant Staphylococcus aureus, 59% of vancomycin- resistant Enterococcus spp. and 88% of penicillin-resistant Streptococcus pneumoniae. The androstane derivative was bactericidal for a variety of other Gram-positive genera, including Nocardia, Corynebacterium and Listeria. Variation in MICs is pH 6-8 media was slight. The frequency of occurrence of bacterial spontaneous mutations to resistance ranged from 10-6 to 10-9. Kill curve analysis confirmed the bactericidal nature of the steroidal amide, and demonstrated that killing was time dependent but not concentration dependent for all organisms. The ability of 3β-acetoxy-17β-(L-prolyl)amino- 5α-androstane to inhibit human cancer cell growth was also evaluated. The concentration required to inhibit 50% of cell growth (GI50) was < 2.5 mg/l for all cell lines examined. In single-dose murine toxicity evaluations, the androstane derivative was non-toxic at doses up to 400 mg/kg. (C) 2000 Elsevier Science B.V. and International Society of Chemotherapy.
AB - The in vitro activity of the steroidal amide 3β-acetoxy-17β-(L- prolyl)amino-5α-androstane against 179 Gram-positive clinical isolates was examined. The minimum bactericidal concentration (MBC)/MIC ratios were ≤ 2 for 73% of methicillin-resistant Staphylococcus aureus, 59% of vancomycin- resistant Enterococcus spp. and 88% of penicillin-resistant Streptococcus pneumoniae. The androstane derivative was bactericidal for a variety of other Gram-positive genera, including Nocardia, Corynebacterium and Listeria. Variation in MICs is pH 6-8 media was slight. The frequency of occurrence of bacterial spontaneous mutations to resistance ranged from 10-6 to 10-9. Kill curve analysis confirmed the bactericidal nature of the steroidal amide, and demonstrated that killing was time dependent but not concentration dependent for all organisms. The ability of 3β-acetoxy-17β-(L-prolyl)amino- 5α-androstane to inhibit human cancer cell growth was also evaluated. The concentration required to inhibit 50% of cell growth (GI50) was < 2.5 mg/l for all cell lines examined. In single-dose murine toxicity evaluations, the androstane derivative was non-toxic at doses up to 400 mg/kg. (C) 2000 Elsevier Science B.V. and International Society of Chemotherapy.
KW - Antibacterial susceptibility
KW - Steroidal amide
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U2 - 10.1016/S0924-8579(00)00156-4
DO - 10.1016/S0924-8579(00)00156-4
M3 - Article
C2 - 10929880
AN - SCOPUS:0033853913
SN - 0924-8579
VL - 15
SP - 299
EP - 304
JO - International Journal of Antimicrobial Agents
JF - International Journal of Antimicrobial Agents
IS - 4
ER -