PMID- 27925693
OWN - NLM
STAT- MEDLINE
DCOM- 20170704
LR  - 20180417
IS  - 1439-7633 (Electronic)
IS  - 1439-4227 (Linking)
VI  - 18
IP  - 4
DP  - 2017 Feb 16
TI  - Identification of N-Arylated NH125 Analogues as Rapid Eradicating Agents against 
      MRSA Persister Cells and Potent Biofilm Killers of Gram-Positive Pathogens.
PG  - 352-357
LID - 10.1002/cbic.201600622 [doi]
AB  - Bacterial biofilms housing dormant persister cells are innately tolerant to 
      antibiotics and disinfectants, yet several membrane-active agents are known to 
      eradicate tolerant bacterial cells. NH125, a membrane-active persister killer and 
      starting point for development, led to the identification of two N-arylated 
      analogues (1 and 2) that displayed improved biofilm eradication potencies 
      compared to the parent compound and rapid persister-cell-killing activities in 
      stationary cultures of methicillin-resistant Staphylococcus aureus (MRSA). We 
      found 1 and 2 to be superior to other membrane-active agents in biofilm 
      eradication assays, with 1 demonstrating minimum biofilm eradication 
      concentrations (MBEC) of 23.5, 11.7, and 2.35 mum against MRSA, 
      methicillin-resistant Staphylococcus epidermidis (MRSE), and vancomycin-resistant 
      Enterococcus faecium (VRE) biofilms, respectively. We tested our panel of 
      membrane-active agents against MRSA stationary cultures and found 1 to rapidly 
      eradicate MRSA stationary cells by 4 log units (99.99 %) in 30 min. The potent 
      biofilm eradication and rapid persister-cell-killing activities exhibited by 
      N-arylated NH125 analogues could have significant impact in addressing 
      biofilm-associated problems.
CI  - (c) 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Abouelhassan, Yasmeen
AU  - Abouelhassan Y
AD  - Department of Medicinal Chemistry, Center for Natural Products Drug Discovery and 
      Development (CNPD3), College of Pharmacy, University of Florida, 1345 Center 
      Drive, Gainesville, FL, 32610, USA.
FAU - Basak, Akash
AU  - Basak A
AD  - Department of Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, 
      FL, 32610, USA.
FAU - Yousaf, Hussain
AU  - Yousaf H
AD  - Department of Medicinal Chemistry, Center for Natural Products Drug Discovery and 
      Development (CNPD3), College of Pharmacy, University of Florida, 1345 Center 
      Drive, Gainesville, FL, 32610, USA.
FAU - Huigens, Robert W 3rd
AU  - Huigens RW 3rd
AD  - Department of Medicinal Chemistry, Center for Natural Products Drug Discovery and 
      Development (CNPD3), College of Pharmacy, University of Florida, 1345 Center 
      Drive, Gainesville, FL, 32610, USA.
AD  - Department of Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, 
      FL, 32610, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170116
PL  - Germany
TA  - Chembiochem
JT  - Chembiochem : a European journal of chemical biology
JID - 100937360
RN  - 0 (Acetamides)
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Imidazoles)
RN  - 0 (N-(4-bromo-2-(2-pyridylcarbonyl)phenyl)-2-aminoacetamide)
RN  - 0 (NH 125)
RN  - 0 (Pyridines)
SB  - IM
MH  - Acetamides/chemistry
MH  - Anti-Bacterial Agents/chemistry/pharmacology
MH  - Biofilms/*drug effects
MH  - Erythrocytes/drug effects
MH  - Gram-Positive Bacteria/*drug effects
MH  - Humans
MH  - Imidazoles/*chemistry/*pharmacology
MH  - Methicillin-Resistant Staphylococcus aureus/*drug effects
MH  - Microbial Sensitivity Tests
MH  - Molecular Structure
MH  - Pyridines/chemistry
OTO - NOTNLM
OT  - MRSA
OT  - antibacterial agents
OT  - biofilms
OT  - drug-resistant bacteria
OT  - persister cells
EDAT- 2016/12/08 06:00
MHDA- 2017/07/05 06:00
CRDT- 2016/12/08 06:00
PHST- 2016/11/16 00:00 [received]
PHST- 2016/12/08 06:00 [pubmed]
PHST- 2017/07/05 06:00 [medline]
PHST- 2016/12/08 06:00 [entrez]
AID - 10.1002/cbic.201600622 [doi]
PST - ppublish
SO  - Chembiochem. 2017 Feb 16;18(4):352-357. doi: 10.1002/cbic.201600622. Epub 2017 
      Jan 16.