Synthesis, Biological Evaluation, Mechanism of Action and Quantitative Structure–Activity Relationship Studies of Chalcones as Antibacterial Agents

<jats:p>Forty‐eight chalcone analogs were synthesized and their <jats:italic>in vitro</jats:italic> antibacterial activity against <jats:italic>Staphylococcus aureus</jats:italic> NCIM 5021, <jats:italic>Bacillus subtilis</jats:italic> NCIM 2718, <jats:italic>Phaseolus vulgaris</jats:italic> NCIM 2813, <jats:italic>Escherichia coli</jats:italic> NCIM 2931, <jats:italic>Salmonella typhi</jats:italic> 2501 and <jats:italic>Enterobacter aerogenes</jats:italic> NCIM 5139 were evaluated by microdilution broth assay. Quantitative structure–activity relationships were developed for all the cases (<jats:italic>r</jats:italic> <jats:sup>2</jats:sup> = 0.68–0.79; <jats:inline-graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="graphic/CBDD_793_mu1.gif" xlink:title="inline image" /> = 0.58–0.78; <jats:italic>q</jats:italic> <jats:sup>2</jats:sup> = 0.51–0.68; <jats:italic>F</jats:italic> = 13.02–61.51). Size, polarizability, electron‐donating/withdrawing and hydrophilic nature of the molecule determine the activity against these Gram‐positive and Gram‐negative bacteria. <jats:italic>Staphylococcus aureus</jats:italic> was the most and <jats:italic>S. typhi</jats:italic> was the least hydrophobic of these organisms. These chalcones act better against more hydrophobic organisms. The more active chalcones have log <jats:italic>P</jats:italic> between 1.5 and 3. Compound <jats:bold>24</jats:bold>, one of the most active compounds, was found to act by damaging the cell wall of <jats:italic>S. aureus.</jats:italic> Slimicidal activity of five of the most active compounds (<jats:bold>24</jats:bold>, <jats:bold>31</jats:bold>, <jats:bold>32</jats:bold>, <jats:bold>34</jats:bold> and <jats:bold>37</jats:bold>) was found to be in the range of 48–60% against <jats:italic>S. aureus</jats:italic> and 40–54% against <jats:italic>E. coli.</jats:italic> A correlation was observed among the hydrophobicity of the compounds, hydrophobicity of the bacterial cell surface and the antibacterial activity of the compound.</jats:p>