Ligand Promiscuity between the Efflux Pumps Human P-Glycoprotein and S. aureus NorA

被引：21

作者：

Brincat, Jean Pierre ^{[1
]}

Broccatelli, Fabio ^{[1
]}

Sabatini, Stefano ^{[2
]}

Frosini, Maria ^{[3
]}

Neri, Annalisa ^{[3
]}

Kaatz, Glenn W. ^{[4
,5
]}

Cruciani, Gabriele ^{[1
]}

Carosati, Emanuele ^{[1
]}

机构：

[1] Univ Perugia, Dipartimento Chim, I-06123 Perugia, Italy

[2] Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06123 Perugia, Italy

[3] Univ Siena, Dept Neurosci, Pharmacol Unit, I-53100 Siena, Italy

[4] Wayne State Univ, Sch Med, Div Infect Dis, Dept Internal Med, Detroit, MI 48201 USA

[5] John D Dingell Dept Vet Affairs Med Ctr, Detroit, MI 48201 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2012年 / 3卷 / 03期

关键词：

Multiple drug resistance; NorA; P-glycoprotein; promiscuous activity; efflux pump inhibitor; S; aureus; GENETICALLY RELATED STRAINS; MULTIDRUG-RESISTANCE; IN-VITRO; INHIBITORS; TRANSPORTER; CIPROFLOXACIN; DERIVATIVES; ASSAYS; CNS;

D O I：

10.1021/ml200293c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Thirty-two diverse compounds were evaluated for their ability to inhibit both Pgp-mediated efflux in mouse T-lymphoma L5178 MDR1 and NorA-mediated efflux in S. aureus SA-1199B. Only four compounds were strong inhibitors of both efflux pumps. Three compounds were found to inhibit Pgp exclusively and strongly, while seven compounds inhibited only NorA. These results demonstrate that Pgp and NorA inhibitors do not necessarily overlap, opening the way to safer therapeutic use of effective NorA inhibitors.

引用

页码：248 / 251

页数：4

共 31 条

[11] A novel inhibitor of multidrug efflux pumps in Staphylococcus aureus [J].

Gibbons, S ;

Oluwatuyi, M ;

Kaatz, GW .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2003, 51 (01) :13-17

[12] Mechanisms of fluoroquinolone resistance in genetically related strains of Staphylococcus aureus [J].

Kaatz, GW ;

Seo, SM .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (12) :2733-2737

[13] Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: Comparison with the effects on CYP3A4 [J].

Katoh, M ;

Nakajima, M ;

Yamazaki, H ;

Yokoi, T .

PHARMACEUTICAL RESEARCH, 2000, 17 (10) :1189-1197

[14] The third-generation P-glycoprotein inhibitor tariquidar may overcome bacterial multidrug resistance by increasing intracellular drug concentration [J].

Leitner, I. ;

Nemeth, J. ;

Feurstein, T. ;

Abrahim, A. ;

Matzneller, P. ;

Lagler, H. ;

Erker, T. ;

Langer, O. ;

Zeitlinger, M. .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2011, 66 (04) :834-839

[15] Use of a genetic approach to evaluate the consequences of inhibition of efflux pumps in Pseudomonas aeruginosa [J].

Lomovskaya, O ;

Lee, A ;

Hoshino, K ;

Ishida, H ;

Mistry, A ;

Warren, MS ;

Boyer, E ;

Chamberland, S ;

Lee, VJ .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (06) :1340-1346

[16] Inhibition of the emergence of ciprofloxacin resistance in Streptococcus pneumoniae by the multidrug efflux inhibitor reserpine [J].

Markham, PN .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1999, 43 (04) :988-989

[17] Structural understanding of efflux-mediated drug resistance: potential routes to efflux inhibition [J].

McKeegan, KS ;

Borges-Walmsley, MI ;

Walmsey, AR .

CURRENT OPINION IN PHARMACOLOGY, 2004, 4 (05) :479-486

[18] Inhibition of antibiotic efflux in bacteria by the novel multidrug resistance inhibitors biricodar (VX-710) and timcodar (VX-853) [J].

Mullin, S ;

Mani, N ;

Grossman, TH .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (11) :4171-4176

[19] Multidrug-resistance efflux pumps - not just for resistance [J].

Piddock, Laura J. V. .

NATURE REVIEWS MICROBIOLOGY, 2006, 4 (08) :629-636

[20] From 6-Aminoquinolone Antibacterials to 6-Amino-7-thiopyranopyridinylquinolone Ethyl Esters as Inhibitors of Staphylococcus aureus Multidrug Efflux Pumps [J].

Pieroni, Marco ;

Dimovska, Mirjana ;

Brincat, Jean Pierre ;

Sabatini, Stefano ;

Carosati, Emanuele ;

Massari, Serena ;

Kaatz, Glenn W. ;

Fravolini, Arnaldo .

JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (11) :4466-4480

← 1 2 3 4 →