Background: Antimicrobial resistance is a persistent problem regarding infection
treatment and calls for developing new antimicrobial agents. Inhibition of bacterial β-ketoacyl acyl
carrier protein synthase III (FabH), which catalyzes the condensation reaction between a CoAattached
acetyl group and an ACP-attached malonyl group in bacteria is an interesting strategy to
find new antibacterial agents.
Objective: The aim of this work was to design and synthesize arylsulfonylhydrazones potentially
FabH inhibitors and evaluate their antimicrobial activity.
Methods: MIC50 values of sulfonylhydrazones against E. coli and S. aureus were determined. Antioxidant
activity was evaluated by DPPH (1-1’-diphenyl-2-picrylhydrazyl) assay and cytotoxicity
against LL24 lung fibroblast cells was verified by MTT method. Principal component analysis
(PCA) was performed in order to suggest a structure-activity relationship. Molecular docking allowed
to propose sulfonylhydrazones interactions with FabH.
Results: The most active compound showed activity against S. aureus and E. coli, with MIC50 =
0.21 and 0.44 μM, respectively. PCA studies correlated better activity to lipophilicity and molecular
docking indicated that sulfonylhydrazone moiety is important to hydrogen-bond with FabH
while methylcatechol ring performs π-π stacking interaction. The DPPH assay revealed that some
sulfonylhydrazones derived from the methylcatechol series had antioxidant activity. None of the
evaluated compounds was cytotoxic to human lung fibroblast cells, suggesting that the compounds
might be considered safe at the tested concentration.
Conclusion: Arylsufonylhydrazones is a promising scaffold to be explored for the design of new