Design, Synthesis and Biological Evaluation of New Piperazin-4-yl-(acetyl-thiazolidine-2,4-dione) Norfloxacin Analogues as Antimicrobial Agents. &nbsp;In an effort to improve the antimicrobial activity of norfloxacin, a series of hybrid norfloxacin-thiazolidinedione molecules were synthesized and screened for their direct antimicrobial activity and their anti-biofilm properties.  The new hybrids were intended to have a new binding mode to DNA gyrase, that will allow for a more potent antibacterial effect, and for activity against current quinolone-resistant bacterial strains.  Moreover, the thiazolidinedione moiety aimed to include additional anti-pathogenicity by preventing biofilm formation.  The resulting compounds showed promising direct activity against Gram-negative strains, and anti-biofilm activity against Gram-positive strains.  Docking studies and ADMET were also used in order to explain the biological properties and revealed some potential advantages over the parent molecule norfloxacin.
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