Influence of fluorination at position 16 of antibacterial pristinamycins II

Chimia

Volumn 58, Issue 3, 2004, Pages 128-132

  Bacqué, Eric ^a  

^a Bat Pasteur   (France)

Author keywords

Antibacterial; DAST; Fluorination; Pristinamycins II

Indexed keywords

ANTIINFECTIVE AGENT; PRISTINAMYCIN; RPR 132552; RPR 202868; STREPTOGRAMIN DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; AQUEOUS SOLUTION; BACTERICIDAL ACTIVITY; CONFERENCE PAPER; CONTROLLED STUDY; COVALENT BOND; DRUG ABSORPTION; DRUG EXCRETION; DRUG INHIBITION; DRUG METABOLISM; DRUG SOLUBILITY; DRUG STABILITY; DRUG SYNTHESIS; FLUORINATION; HUMAN; HUMAN CELL; IC 50; MINIMUM INHIBITORY CONCENTRATION; MOUSE; NONHUMAN; PH MEASUREMENT;

EID: 1842785058     PISSN: 00094293     EISSN: None     Source Type: Journal    
DOI: 10.2533/000942904777678109     Document Type: Conference Paper

References (14)

1. a) R. Bax, N. Mullan, J. Verhoef, Int. J. Antimicrob. Agents 2000, 16, 51.
2. b) E.L. Setti, L. Quattrochio, R.G. Micetich. Drugs of the Future 1997, 22, 271.
3. c) D.T.W. Chu, J.J. Plattner, L. Katz, J. Med. Chem. 1996, 39, 3853.
4. J.M. Paris, J.C. Barrière, C. Smith, P.E. Bost, "The Chemistry of Pristinamycins", in "Recent Progress in the Chemical Synthesis of Antibiotics", Ed. G. Lukacs, M. Ohno, Springer Verlag, Berlin, Heidelberg, New York, 1991, 183.
5. V. Loncle, A. Casetta, A. Buu-Hoï, N. El Solh, Antimicrob. Agents Chemother. 1993, 37, 2159.
6. J.C. Barrière, D.H. Bouanchaud, J.M. Paris, O. Rolin, N.V. Harris, C. Smith, J. Antimicrob. Chemother. 1992, 30 (suppl.A): 1.
7. J.C. Barrière, J.M. Paris, Drugs of the Future 1993, 18 (9), 833.
8. J.C. Barrière, D. Bouanchaud, J.F. Desnottes, J.M. Paris, Expert Opinion Invest. Drugs 1994, 3 (2), 115.
9. B. Ronan, E. Bacqué, J.C. Barrière, S. Sablé, Tetrahedron 2003, 59, 2929.
10. In the poly(U) assay, an artificial mRNA, poly(U), coding only for one amino acid (phenylalanine), is translated and the incorporation of radioactive-labeled phenylalanine into protein (poly[Phe]) is measured. The results are expressed as IC50 values, corresponding to the concentration, expressed in μM, at which 50% of the cell-free poly(Phe) synthesis is blocked. See for more details: 'The ribosome, structure, function and evolution', Ed. W.E. Hill, A. Dahlberg, R.A. Garrett, P.B. Moore, D. Schlessinger, J.R. Warner, American Society for Microbiology Washington, D.C., 1990, chapter 2, 56-70.
11. The method used to determine MICs was in accordance with the NCCLS recommendations (approved standard M7-A2; National Committee for Laboratory Standards, Villanova, Pa., USA. 1992): two-fold dilutions of antibiotic in sterile distilled water were prepared from stock solutions in appropriate solvent and incorporated into appropriate agar media varying with the bacterial species studied. A Denley multipoint inoculator was used to apply spots of about 104 colony-forming units (cfu) of each strain tested to plates. Inoculated plates were incubated at 37°C in conditions appropriate to the bacterial species studied. After incubation, the minimal inhibitory concentration (MIC) was defined as the lowest concentration in mg/l that completely inhibited the growth of bacteria.
12. Mice 0F1 weighing 20±2 g were used for all experiments (3 to 6 males + 3 to 6 females per group). Experimental systemic infections were established by intraperitoneal injection of bacteria diluted so as to obtain an inoculum between 10 and 100 times the lethal dose. Mice were treated orally or subcutaneously by the new associations PIB/PIIs (30/70 w/w). At 7 days post-infection, the effective dose 50% (ED50) values were calculated as described by G.J. Miraglia, 'Chemotherapy of Infectious Diseases', Ed. H.H. Gadebush, C.R.C. Press, 1976, 1. The ED50 was defined as the dose that protected 50% of treated mice when all the controls died.
13. M. Aumercier, S. Boukallab, M.L. Capmau, F. Le Goffic, J. Antimicrob. Chemother. 1986, 39, 9.
14. In-house results for natural PIIs; for RPR132552, this compound was only metabolized by CYP3A4, with an estimated apparent Km of 2.5 μM.