PMID- 27245927
OWN - NLM
STAT- MEDLINE
DCOM- 20180115
LR  - 20180115
IS  - 1521-3765 (Electronic)
IS  - 0947-6539 (Linking)
VI  - 22
IP  - 27
DP  - 2016 Jun 27
TI  - Synthetically Tuning the 2-Position of Halogenated Quinolines: Optimizing 
      Antibacterial and Biofilm Eradication Activities via Alkylation and Reductive 
      Amination Pathways.
PG  - 9181-9
LID - 10.1002/chem.201600926 [doi]
AB  - Agents capable of eradicating bacterial biofilms are of great importance to human 
      health as biofilm-associated infections are tolerant to our current antibiotic 
      therapies. We have recently discovered that halogenated quinoline (HQ) small 
      molecules are: 1) capable of eradicating methicillin-resistant Staphylococcus 
      aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and 
      vancomycin-resistant Enterococcus faecium (VRE) biofilms, and 2) synthetic tuning 
      of the 2-position of the HQ scaffold has a significant impact on antibacterial 
      and antibiofilm activities. Here, we report the chemical synthesis and biological 
      evaluation of 39 HQ analogues that have a high degree of structural diversity at 
      the 2-position. We identified diverse analogues that are alkylated and aminated 
      at the 2-position of the HQ scaffold and demonstrate potent antibacterial 
      (MIC</=0.39 mum) and biofilm eradication (MBEC 1.0-93.8 mum) activities against 
      drug-resistant Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus 
      faecium strains while demonstrating <5 % haemolysis activity against human red 
      blood cells (RBCs) at 200 mum. In addition, these HQs demonstrated low 
      cytotoxicity against HeLa cells. Halogenated quinolines are a promising class of 
      antibiofilm agents against Gram-positive pathogens that could lead to useful 
      treatments against persistent bacterial infections.
CI  - (c) 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Basak, Akash
AU  - Basak A
AD  - Department of Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, 
      FL, 32610, USA.
FAU - Abouelhassan, Yasmeen
AU  - Abouelhassan Y
AD  - Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery 
      and Development (CNPD3), University of Florida, 1345 Center Drive, Gainesville, 
      FL, 32610, USA.
FAU - Norwood, Verrill M 4th
AU  - Norwood VM 4th
AD  - Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery 
      and Development (CNPD3), University of Florida, 1345 Center Drive, Gainesville, 
      FL, 32610, USA.
FAU - Bai, Fang
AU  - Bai F
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, FL, 32610, USA.
FAU - Nguyen, Minh Thu
AU  - Nguyen MT
AD  - Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery 
      and Development (CNPD3), University of Florida, 1345 Center Drive, Gainesville, 
      FL, 32610, USA.
FAU - Jin, Shouguang
AU  - Jin S
AD  - Department of Molecular Genetics and Microbiology, University of Florida, 
      Gainesville, FL, 32610, USA.
FAU - Huigens, Robert W 3rd
AU  - Huigens RW 3rd
AD  - Department of Chemistry, University of Florida, 1600 SW Archer Road, Gainesville, 
      FL, 32610, USA. rhuigens@cop.ufl.edu.
AD  - Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery 
      and Development (CNPD3), University of Florida, 1345 Center Drive, Gainesville, 
      FL, 32610, USA. rhuigens@cop.ufl.edu.
LA  - eng
PT  - Journal Article
DEP - 20160601
PL  - Germany
TA  - Chemistry
JT  - Chemistry (Weinheim an der Bergstrasse, Germany)
JID - 9513783
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Quinolines)
SB  - IM
MH  - Alkylation
MH  - Amination
MH  - Anti-Bacterial Agents/*chemical synthesis/pharmacology/toxicity
MH  - Biofilms/drug effects
MH  - Cell Survival/drug effects
MH  - Drug Resistance, Bacterial/drug effects
MH  - Enterococcus faecium/drug effects/physiology
MH  - Erythrocytes/cytology/drug effects/metabolism
MH  - Halogenation
MH  - HeLa Cells
MH  - Hemolysis/drug effects
MH  - Humans
MH  - Methicillin-Resistant Staphylococcus aureus/drug effects/physiology
MH  - Quinolines/*chemistry/pharmacology/toxicity
MH  - Staphylococcus/drug effects
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - antibiotic tolerance
OT  - bacterial biofilms
OT  - halogenated quinolone
OT  - medicinal chemistry
OT  - structure-activity relationships
EDAT- 2016/06/02 06:00
MHDA- 2018/01/16 06:00
CRDT- 2016/06/02 06:00
PHST- 2016/02/26 00:00 [received]
PHST- 2016/06/02 06:00 [entrez]
PHST- 2016/06/02 06:00 [pubmed]
PHST- 2018/01/16 06:00 [medline]
AID - 10.1002/chem.201600926 [doi]
PST - ppublish
SO  - Chemistry. 2016 Jun 27;22(27):9181-9. doi: 10.1002/chem.201600926. Epub 2016 Jun 
      1.