Abstract
In this study, we tested five compounds belonging to a novel series of piperazine arylideneimidazolones for the ability to inhibit the AcrAB-TolC efflux pump. The biphenylmethylene derivative (BM-19) and the fluorenylmethylene derivative (BM-38) were found to possess the strongest efflux pump inhibitor (EPI) activities in the AcrAB-TolC-overproducingEscherichia colistrain 3-AG100, whereas BM-9, BM-27, and BM-36 had no activity at concentrations of up to 50 μM in a Nile red efflux assay. MIC microdilution assays demonstrated that BM-19 at 1/4 MIC (intrinsic MIC, 200 μM) was able to reduce the MICs of levofloxacin, oxacillin, linezolid, and clarithromycin 8-fold. BM-38 at 1/4 MIC (intrinsic MIC, 100 μM) was able to reduce only the MICs of oxacillin and linezolid (2-fold). Both compounds markedly reduced the MIC of rifampin (BM-19, 32-fold; and BM-38, 4-fold), which is suggestive of permeabilization of the outer membrane as an additional mechanism of action. Nitrocefin hydrolysis assays demonstrated that in addition to their EPI activity, both compounds were in fact weak permeabilizers of the outer membrane. Moreover, it was found that BM-19, BM-27, BM-36, and BM-38 acted as near-infrared-emitting fluorescent membrane probes, whic...Continue Reading
References
Jan 30, 1999·Antimicrobial Agents and Chemotherapy·T KöhlerJ C Pechere
Mar 18, 2000·Antimicrobial Agents and Chemotherapy·W V KernS B Levy
Dec 20, 2000·Antimicrobial Agents and Chemotherapy·O LomovskayaV J Lee
Jul 19, 2001·Bioorganic & Medicinal Chemistry Letters·A ThorarensenB H Yagi
Mar 21, 2002·Il Farmaco·Ewa SzymańskaAndrzej Kasprowicz
Jun 13, 2002·Il Farmaco·Ewa Szymańska, Katarzyna Kieć-Kononowicz
Jan 28, 2005·Antimicrobial Agents and Chemotherapy·Jürgen A Bohnert, Winfried V Kern
Aug 13, 2008·Antimicrobial Agents and Chemotherapy·Andrew M BaileyLaura J V Piddock
Feb 18, 2010·Antimicrobial Agents and Chemotherapy·Siew Ping Lim, Hiroshi Nikaido
Mar 23, 2010·The Journal of Antimicrobial Chemotherapy·Laura J V PiddockSimon Gibbons
Jul 8, 2010·Antimicrobial Agents and Chemotherapy·Jürgen A BohnertHiroshi Nikaido
Nov 13, 2010·Bioscience, Biotechnology, and Biochemistry·Bo ZengZhongbin Guan
Jan 5, 2011·International Journal of Antimicrobial Agents·Mark I GarveyLaura J V Piddock
Jun 24, 2011·PloS One·Jürgen A BohnertWinfried V Kern
Jun 28, 2011·The Journal of Antimicrobial Chemotherapy·Jürgen A BohnertWinfried V Kern
Jun 29, 2011·FEMS Microbiology Reviews·Hiroshi Nikaido, Jean-Marie Pagès
Jan 13, 2012·Journal of Clinical Microbiology·R P RennieJ Cloke
Apr 6, 2013·The Open Microbiology Journal·Jürgen A BohnertWinfried V Kern
Nov 10, 2013·Current Topics in Medicinal Chemistry·Paolo RuggeroneAttilio V Vargiu
Nov 20, 2013·Antimicrobial Agents and Chemotherapy·Timothy J OppermanTerry L Bowlin
Jul 16, 2014·PloS One·Vasudevan AparnaWaheeta Hopper
Sep 4, 2014·Antimicrobial Agents and Chemotherapy·Sabine SchusterWinfried V Kern
Mar 31, 2015·Bioorganic & Medicinal Chemistry·Son T NguyenTimothy J Opperman
Citations
May 21, 2016·Frontiers in Microbiology·Ewa Otręebska-MachajSandrine Alibert
Mar 16, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gabriella SpenglerLeonard Amaral
Jun 27, 2017·Journal of Medicinal Chemistry·Keith M HaynesJohn K Walker
Sep 11, 2018·Expert Opinion on Drug Discovery·Paula BlancoManuel Alcalde-Rico
Aug 22, 2018·Infection and Immunity·Yuehui ZhuJames M Fleckenstein
Jan 30, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aneta KaczorJadwiga Handzlik
Feb 13, 2019·FEMS Microbiology Letters·Dahyun Hwang, Young-Hee Lim
Dec 6, 2017·Acta Crystallographica. Section C, Structural Chemistry·Ewa ŻesławskaJadwiga Handzlik
May 15, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aneta KaczorJadwiga Handzlik
Aug 24, 2019·BMC Microbiology·Srijan JindalDouglas B Kell
May 19, 2017·PeerJ·Diana MachadoMiguel Viveiros
Nov 7, 2018·Acta Crystallographica. Section C, Structural Chemistry·Ewa ŻesławskaJadwiga Handzlik
May 3, 2018·MSystems·Lauren E BrooksMark J Sistrom
Nov 18, 2020·Antimicrobial Agents and Chemotherapy·Sabine SchusterWinfried V Kern
Dec 6, 2019·European Journal of Medicinal Chemistry·Yinhu WangShutao Ma
Dec 15, 2019·Bioorganic & Medicinal Chemistry Letters·Bec J RoldanLarryn W Peterson
Feb 21, 2021·Scientific Reports·Erika BoulantJean Michel Bolla
Dec 7, 2020·European Journal of Medicinal Chemistry·Yinhu WangShutao Ma
Mar 7, 2021·International Journal of Molecular Sciences·Aneta KaczorJadwiga Handzlik
May 1, 2021·Antibiotics·Sabine SchusterWinfried V Kern
May 4, 2021·Current Opinion in Microbiology·Helen I ZgurskayaPaolo Ruggerone