New pyridoquinoline derivatives as potential inhibitors of the fluoroquinolone efflux pump in resistant Enterobacter aerogenes strains

被引：79

作者：

Chevalier, J

Atifi, S

Eyraud, A

Mahamoud, A

Barbe, J

Pagès, JM

机构：

[1] Univ Mediterranee, Fac Med, F-13385 Marseille 05, France

[2] Univ Mediterranee, Fac Pharm, CNRS, UMR 6009,GERCTOP, F-13385 Marseille, France

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 23期

关键词：

D O I：

10.1021/jm010911z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Enterobacter aerogenes, one of the most frequently isolated nosocomial pathogens in France, is exhibiting increasing multidrug resistance mechanisms associated with a change in membrane permeability. For drugs of the quinolone family, mutations in the target and active efflux play a prominent role in the resistance. We report here the effect of several pyridoquinoline derivatives that restore a noticeable fluoroquinolone accumulation to resistant strains that overexpress the MarA activator. Studies of the energy-dependent quinolone efflux indicate that the most efficient derivatives tested probably inhibit the resistance process by acting as substrate competitors on the pump extruding intracellular norfloxacin.

引用

收藏

页码：4023 / 4026

页数：4

相关论文

共 32 条

[21] THE SYNTHESIS OF PYRIDOQUINOLINES WITH DIALKYLAMINOPROPYLAMINE SIDE-CHAINS [J].

MOLOCK, FF ;

BOYKIN, DW .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1983, 20 (03) :681-686

[22] INHIBITION OF THE TETRACYCLINE EFFLUX ANTIPORT PROTEIN BY 13-THIO-SUBSTITUTED 5-HYDROXY-6-DEOXYTETRACYCLINES [J].

NELSON, ML ;

PARK, BH ;

ANDREWS, JS ;

GEORGIAN, VA ;

THOMAS, RC ;

LEVY, SB .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (03) :370-377

[23] Reversal of tetracycline resistance mediated by different bacterial tetracycline resistance determinants by an inhibitor of the Tet(B) antiport protein [J].

Nelson, ML ;

Levy, SB .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (07) :1719-1724

[24] EFFLUX-MEDIATED MULTIDRUG RESISTANCE IN BACILLUS-SUBTILIS - SIMILARITIES AND DISSIMILARITIES WITH THE MAMMALIAN SYSTEM [J].

NEYFAKH, AA ;

BIDNENKO, VE ;

CHEN, LB .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (11) :4781-4785

[25] Multidrug efflux pumps of gram-negative bacteria [J].

Nikaido, H .

JOURNAL OF BACTERIOLOGY, 1996, 178 (20) :5853-5859

[26] PREVENTION OF DRUG ACCESS TO BACTERIAL TARGETS - PERMEABILITY BARRIERS AND ACTIVE EFFLUX [J].

NIKAIDO, H .

SCIENCE, 1994, 264 (5157) :382-388

[27] AcrAB efflux pump plays a major role in the antibiotic resistance phenotype of Escherichia coli multiple-antibiotic-resistance (Mar) mutants [J].

Okusu, H ;

Ma, D ;

Nikaido, H .

JOURNAL OF BACTERIOLOGY, 1996, 178 (01) :306-308

[28] Inhibitors of efflux pumps in Pseudomonas aeruginosa potentiate the activity of the fluoroquinolone antibacterial levofloxacin [J].

Renau, TE ;

Léger, R ;

Flamme, EM ;

Sangalang, J ;

She, MW ;

Yen, R ;

Gannon, CL ;

Griffith, D ;

Chamberland, S ;

Lomovskaya, O ;

Hecker, SJ ;

Lee, VJ ;

Ohta, T ;

Nakayama, K .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (24) :4928-4931

[29] The effect of reserpine, an inhibitor of multidrug efflux pumps, on the in-vitro activities of ciprofloxacin, sparfloxacin and moxifloxacin against clinical isolates of Staphylococcus aureus [J].

Schmitz, FJ ;

Fluit, AC ;

Lückefahr, M ;

Engler, B ;

Hofmann, B ;

Verhoef, J ;

Heinz, HP ;

Hadding, U ;

Jones, ME .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1998, 42 (06) :807-810

[30] RESISTANCE TO ANTIBIOTICS MEDIATED BY TARGET ALTERATIONS [J].

SPRATT, BG .

SCIENCE, 1994, 264 (5157) :388-393

← 1 2 3 4 →