Antimicrobial and cancer cell growth inhibitory activities of 3beta-acetoxy-17beta-(L-prolyl)amino-5alpha-androstane in vitro.
The in vitro activity of the steroidal amide 3beta-acetoxy-17beta-(L-prolyl)amino-5alpha-androstane against 179 gram-positive clinical isolates was examined. The minimum bactericidal concentration (MBC)/MIC ratios were < or = 2 for 73% of methicillin-resistant Staphyllococcus 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 3beta-acetoxy-17beta-(L-prolyl)amino-5alpha-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.
Pettit
R K
RK
Department of Microbiology, Cancer Research Institute, Arizona State University, Tempe 85287-1604, USA. pettitr@asu.edu
Cage
G D
GD
Pettit
G R
GR
Liebman
J A
JA
D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D005260:Female; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C417166:3-acetoxy-17-prolylaminoandrostane; D000731:Androstanes; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D011392:Proline