Antimicrobial and cancer cell growth inhibitory activities of 3 beta-acetoxy-17 beta-(L-prolyl)amino-5 alpha-androstane in vitro

The in vitro activity of the steroidal amide 3 beta-acetoxy-17 beta-(L-prol yl)amino-5 alpha-androstane against 179 Gram-positive clinical isolates was examined. The minimum bactericidal concentration (MBC)MIC ratios were less than or equal to 2 for 73% of methicillin-resistant Staphylocuccus aureus, 59% of vancomycin-resistant Enterococcus spp. and 88% of penicillin-resist ant Streptococcus pneumoniae. The androstant derivative was bactericidal fo r a variety of other Gram-positive genera, including Nocardia, Corynebacter ium and Listeria. Variation in MICs is pH 6-8 media was slight. The frequen cy of occurrence of bacterial spontaneous mutations to resistance ranged fr om 10(-6) to 10(-9). Kill curve analysis confirmed the bactericidal nature of the steroidal amide, and demonstrated that killing was time dependent bu t not concentration dependent for all organisms. The ability of 3 beta-acet oxy-17 beta-(L-prolyl)amino-5 alpha-androstane to inhibit human cancer cell growth was also evaluated. The concentration required to inhibit 50%, of c ell growth (GI(50)) was <2.5 mg/l For all cell lines examined. Tn single-do se murine toxicity evaluations, the androstane derivative was non-toxic at doses up to 400 mg/kg. (C) 2000 Elsevier Science B.V. and International Soc iety of Chemotherapy. All rights reserved.