Synthesis and Antimicrobial Evaluation of Amphiphilic Neamine Derivatives

被引:61
作者
Baussanne, Isabelle [1 ]
Bussiere, Antoine [1 ]
Halder, Somnath [1 ]
Ganem-Elbaz, Carine [2 ]
Ouberai, Myriam [3 ]
Riou, Mickael [3 ]
Paris, Jean-Marc [2 ]
Ennifar, Eric [4 ]
Mingeot-Leclereq, Marie-Paule [3 ]
Decout, Jean-Luc [1 ]
机构
[1] Univ Grenoble 1, CNRS, UMR 5063, Dept Pharmacochim Mol,ICMG FR 2607, F-38041 Grenoble, France
[2] Ecole Natl Super Chim Paris, CNRS, UMR 7573, Paris, France
[3] Catholic Univ Louvain, Louvain Drug Res Inst, LDRI, Unite Pharmacol Cellulaire & Mol,FACM, B-1200 Brussels, Belgium
[4] Univ Strasbourg, CNRS, Inst Biol Mol & Cellulaire, Architecture & React ARN, Strasbourg, France
关键词
OUTER-MEMBRANE PERMEABILITY; RIBOSOMAL-RNA METHYLATION; HIV-1 TAR RNA; AMINOGLYCOSIDE ANTIBIOTICS; A-SITE; PSEUDOMONAS-AERUGINOSA; MOLECULAR-BASIS; RESISTANCE; BINDING; COMPLEXES;
D O I
10.1021/jm900615h
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The aminoglycoside antibiotics bind to the 16S bacterial rRNA and disturb the protein synthesis. One to four hydroxyl functions of the small aminoglycoside neamine were capped with phenyl, naphthyl, pyridyl, or quinolyl rings. The 3',4- (6), 3',6- (7a), and the 3',4',6- (10a) 2-naphthylmethylene derivatives appeared to be active against sensitive and resistant Staphylococcus aureus strains. 10a also showed marked antibacterial activities against Gram (-) bacteria, including strains expressing enzymes modifying aminoglycosides, efflux pumps, or rRNA methylases. 7a and 10a revealed a weak and aspecific binding to a model bacterial 16S rRNA. Moreover, its compared to neomycin B, 10a showed a lower ability to decrease H-3 leucine incorporation into proteins in Pseudomonas aeruginosa. All together, out, results suggest that the 3',4,6-tri-2-naphthylmethylene neamine derivative 10a should act against Gram (-) bacteria through it mechanism different from inhibition of protein synthesis, probably by membrane destabilization.
引用
收藏
页码:119 / 127
页数:9
相关论文
共 33 条
[1]   Dimeric aminoglycosides as antibiotics [J].
Agnelli, T ;
Sucheck, SJ ;
Marby, KA ;
Rabuka, D ;
Yao, SL ;
Sears, PS ;
Liang, FS ;
Wong, CH .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (12) :1562-1566
[2]   Design, synthesis, and antibacterial activities of neomycin-lipid conjugates: Polycationic lipids with potent gram-positive activity [J].
Bera, Smritilekha ;
Zhanel, George G. ;
Schweizer, Frank .
JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (19) :6160-6164
[3]   Aminoglycoside binding to the HIV-1 RNA dimerization initiation site: thermodynamics and effect on the kissing-loop to duplex conversion [J].
Bernacchi, Serena ;
Freisz, Severine ;
Maechling, Clarisse ;
Spiess, Bernard ;
Marquet, Roland ;
Dumas, Philippe ;
Ennifar, Eric .
NUCLEIC ACIDS RESEARCH, 2007, 35 (21) :7128-7139
[4]   Structural basis for aminoglycoside inhibition of bacterial ribosome recycling [J].
Borovinskaya, Maria A. ;
Pai, Raj D. ;
Zhang, Wen ;
Schuwirth, Barbara S. ;
Holton, James M. ;
Hirokawa, Go ;
Kaji, Hideko ;
Kaji, Akira ;
Cate, Jamie H. Doudna .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (08) :727-732
[5]   Bacterial enzymatic resistance:: β-lactamases and aminoglycoside-modifying enzymes [J].
Bush, K ;
Miller, GH .
CURRENT OPINION IN MICROBIOLOGY, 1998, 1 (05) :509-515
[6]   Gram-negative outer and inner membrane models: Insertion of cyclic cationic lipopeptides [J].
Clausell, Adria ;
Garcia-Subirats, Maria ;
Pujol, Montserrat ;
Busquets, M. Antonia ;
Rabanal, Francesc ;
Cajal, Yolanda .
JOURNAL OF PHYSICAL CHEMISTRY B, 2007, 111 (03) :551-563
[7]  
*CLIN LAB STAND I, 2007, M7A7 CLIN LAB STAN S, V27
[8]   16S ribosomal RNA methylation: Emerging resistance mechanism against aminoglycosides [J].
Doi, Yohei ;
Arakawa, Yoshichika .
CLINICAL INFECTIOUS DISEASES, 2007, 45 (01) :88-94
[9]   Binding of neomycin-class aminoglycoside antibiotics to the A-site of 16 S rRNA [J].
Fourmy, D ;
Recht, MI ;
Puglisi, JD .
JOURNAL OF MOLECULAR BIOLOGY, 1998, 277 (02) :347-362
[10]   Crystal structures of complexes between aminoglycosides and decoding A site oligonucleotides:: role of the number of rings and positive charges in the specific binding leading to miscoding [J].
François, B ;
Russell, RJM ;
Murray, JB ;
Aboul-ela, F ;
Masquida, B ;
Vicens, Q ;
Westhof, E .
NUCLEIC ACIDS RESEARCH, 2005, 33 (17) :5677-5690