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A Detailed Study of Antibacterial 3‐Acyltetramic Acids and 3‐Acylpiperidine‐2,4‐diones
Author(s) -
Jeong YongChul,
Bikadi Zsolt,
Hazai Eszter,
Moloney Mark G.
Publication year - 2014
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201402093
Subject(s) - antibacterial activity , combinatorial chemistry , chemistry , rna polymerase , stereochemistry , acylation , gram , drug discovery , structure–activity relationship , bacteria , biological activity , biochemistry , biology , escherichia coli , gene , in vitro , genetics , catalysis
Inspired by the core fragment of antibacterial natural products such as streptolydigin, 3‐acyltetramic acids and 3‐acylpiperidine‐2,4‐diones have been synthesised from the core heterocycle by direct acylation with the substituted carboxylic acids using a strategy which permits ready access to a structurally diverse compound library. The antibacterial activity of these systems has been established against a panel of Gram‐positive and Gram‐negative bacteria, with activity mostly against the former, which in some cases is very potent. Data consistent with modes of action against undecaprenylpyrophosphate synthase (UPPS) and/or RNA polymerase (RNAP) for a small subset of the library has been obtained. The most active compounds have been shown to exhibit binding at known binding sites of streptolydigin and myxopyronin at UPPS and RNAP. These systems offer potential for their antibacterial activity, and further demonstrate the use of natural products as biologically validated starting points for drug discovery.