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PDBsum entry 3dp1
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References listed in PDB file
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Key reference
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Title
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Discovering potent inhibitors against the beta-Hydroxyacyl-Acyl carrier protein dehydratase (fabz) of helicobacter pylori: structure-Based design, Synthesis, Bioassay, And crystal structure determination.
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Authors
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L.He,
L.Zhang,
X.Liu,
X.Li,
M.Zheng,
H.Li,
K.Yu,
K.Chen,
X.Shen,
H.Jiang,
H.Liu.
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Ref.
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J Med Chem, 2009,
52,
2465-2481.
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PubMed id
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Abstract
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The discovery of HpFabZ inhibitors is now of special interest in the treatment
of various gastric diseases. In this work, three series of derivatives
(compounds 3, 4, and 5) were designed, synthesized, and their biological
activities were investigated as potential HpFabZ inhibitors in a two phased
manner. First, we designed and synthesized two series of derivatives (3a-r and
4a-u) and evaluated the enzyme-based assay against HpFabZ. Five compounds (3i-k,
3m, and 3q) showed potential inhibitory activity, with IC(50) values less than 2
muM. Second, a focused combinatorial library containing 280 molecules was
designed employing the LD1.0 program. Twelve compounds (5a-l) were selected and
synthesized. The activity of the most potent compound 5h (IC(50) = 0.86 muM) was
46 times higher than that of the hit 1. The high hit rate and the potency of the
new HpFabZ inhibitors demonstrated the efficiency of the strategy for the
focused library design and virtual screening.
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