PMID- 26102297
OWN - NLM
STAT- MEDLINE
DCOM- 20151012
LR  - 20150723
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 58
IP  - 14
DP  - 2015 Jul 23
TI  - Membrane Active Small Molecules Show Selective Broad Spectrum Antibacterial 
      Activity with No Detectable Resistance and Eradicate Biofilms.
PG  - 5486-500
LID - 10.1021/acs.jmedchem.5b00443 [doi]
AB  - Treating bacterial biofilms with conventional antibiotics is limited due to 
      ineffectiveness of the drugs and higher propensity to develop bacterial 
      resistance. Development of new classes of antibacterial therapeutics with 
      alternative mechanisms of action has become imperative. Herein, we report the 
      design, synthesis, and biological evaluations of novel membrane-active small 
      molecules featuring two positive charges, four nonpeptidic amide groups, and 
      variable hydrophobic/hydrophilic (amphiphilic) character. The biocides 
      synthesized via a facile methodology not only displayed good antibacterial 
      activity against wild-type bacteria but also showed high activity against various 
      drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus 
      (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and beta-lactam-resistant 
      Klebsiella pneumoniae. Further, these biocides not only inhibited the formation 
      of biofilms but also disrupted the established S. aureus and E. coli biofilms. 
      The membrane-active biocides hindered the propensity to develop bacterial 
      resistance. Moreover, the biocides showed negligible toxicity against mammalian 
      cells and thus bear potential to be used as therapeutic agents.
FAU - Hoque, Jiaul
AU  - Hoque J
AD  - Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, 
      Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 
      560064, India.
FAU - Konai, Mohini M
AU  - Konai MM
AD  - Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, 
      Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 
      560064, India.
FAU - Gonuguntla, Spandhana
AU  - Gonuguntla S
AD  - Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, 
      Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 
      560064, India.
FAU - Manjunath, Goutham B
AU  - Manjunath GB
AD  - Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, 
      Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 
      560064, India.
FAU - Samaddar, Sandip
AU  - Samaddar S
AD  - Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, 
      Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 
      560064, India.
FAU - Yarlagadda, Venkateswarlu
AU  - Yarlagadda V
AD  - Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, 
      Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 
      560064, India.
FAU - Haldar, Jayanta
AU  - Haldar J
AD  - Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, 
      Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru 
      560064, India.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150709
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Small Molecule Libraries)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Anti-Bacterial Agents/*chemistry/*pharmacology/toxicity
MH  - Bacteria/cytology/drug effects
MH  - Biofilms/*drug effects/growth & development
MH  - Cell Membrane/*drug effects
MH  - Drug Resistance, Bacterial/*drug effects
MH  - HEK293 Cells
MH  - Hemolysis/drug effects
MH  - Humans
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Intracellular Space/drug effects/metabolism
MH  - Kinetics
MH  - Membrane Potentials/drug effects
MH  - Microbial Sensitivity Tests
MH  - Permeability/drug effects
MH  - Potassium/metabolism
MH  - Small Molecule Libraries/*chemistry/*pharmacology/toxicity
MH  - Structure-Activity Relationship
EDAT- 2015/06/24 06:00
MHDA- 2015/10/13 06:00
CRDT- 2015/06/24 06:00
PHST- 2015/06/24 06:00 [entrez]
PHST- 2015/06/24 06:00 [pubmed]
PHST- 2015/10/13 06:00 [medline]
AID - 10.1021/acs.jmedchem.5b00443 [doi]
PST - ppublish
SO  - J Med Chem. 2015 Jul 23;58(14):5486-500. doi: 10.1021/acs.jmedchem.5b00443. Epub 
      2015 Jul 9.