G Model
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In conclusion, two series of novel LpxC inhibitors containing the
terminal kojic acid derivatives and methylsulfone were synthe-
sized and evaluated. The MIC values indicated that the length of
the hydrophobic tail played an important role and the compounds
with diphenylacetylene scaffold exhibited best antibacterial
activities. In series 1, most of the compounds lost their antibacte-
rial activities and the introduction of kojic acid derivatives did not
provide extra improvement of antibacterial activities obviously
compared to CHIR-090 and LPC-011 under low-iron condition.
In series 2, some compounds, especially 22b and c, exhibited
comparable antibacterial activities to CHIR-090 against E. coli and
P. aeruginosa and better metabolic stability than CHIR-090 and
LPC-011 in liver microsomes (rat and mouse). These results
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manifested the terminal methylsulfone may be
a preferred
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Acknowledgments
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conformations of LpxC: implications for antibiotic design, Chem. Biol. 18 201
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We are grateful to National Science and Technology Major
Project for the support of this research. The project described was
(2011) 38–47.
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LpxC inhibitors based on the diacetylene scaffold, Bioorg. Med. Chem. 19 (2011) 204
162 Q2 supported by Key New Drug Creation and Manufacturing Program,
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852–860.
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China (No. 2014ZX09507009-016).
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Appendix A. Supplementary data
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Supplementary data associated with this article can be found, in
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Antimicrob. Agents Chemother. 54 (2010) 2291–2302.
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Please cite this article in press as: S. Ding, et al., Design, synthesis and biological evaluation of LpxC inhibitors with novel hydrophilic