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PDBsum entry 4glw
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Ligase/ligase inhibitor
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PDB id
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4glw
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References listed in PDB file
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Key reference
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Title
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Structure-Guided design, Synthesis and biological evaluation of novel DNA ligase inhibitors with in vitro and in vivo anti-Staphylococcal activity.
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Authors
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J.P.Surivet,
R.Lange,
C.Hubschwerlen,
W.Keck,
J.L.Specklin,
D.Ritz,
D.Bur,
H.Locher,
P.Seiler,
D.S.Strasser,
L.Prade,
C.Kohl,
C.Schmitt,
G.Chapoux,
E.Ilhan,
N.Ekambaram,
A.Athanasiou,
A.Knezevic,
D.Sabato,
A.Chambovey,
M.Gaertner,
M.Enderlin,
M.Boehme,
V.Sippel,
P.Wyss.
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Ref.
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Bioorg Med Chem Lett, 2012,
22,
6705-6711.
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PubMed id
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Abstract
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A series of 2-amino-[1,8]-naphthyridine-3-carboxamides (ANCs) with potent
inhibition of bacterial NAD(+)-dependent DNA ligases (LigAs) evolved from a
2,4-diaminopteridine derivative discovered by HTS. The design was guided by
several highly resolved X-ray structures of our inhibitors in complex with
either Streptococcus pneumoniae or Escherichia coli LigA. The
structure-activity-relationship based on the ANC scaffold is discussed. The
in-depth characterization of
2-amino-6-bromo-7-(trifluoromethyl)-[1,8]-naphthyridine-3-carboxamide, which
displayed promising in vitro (MIC Staphylococcus aureus 1mg/L) and in vivo
anti-staphylococcal activity, is presented.
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