Design, synthesis and antibacterial activity of cinnamaldehyde derivatives as inhibitors of the bacterial cell division protein FtsZ

• DOI: 10.1016/j.ejmech.2015.04.048
• Publication Date: 2015-04-26T00:04:40Z
• Authors: Xin Li; Juzheng Sheng; Guihua Huang; Ruixin Ma; Fengxin Yin; Di Song; Can Zhao; Shutao Ma
• Keywords: 0301 basic medicine; Cytoskeletal Proteins; Staphylococcus aureus; 03 medical and health sciences; Bacterial Proteins; Molecular Structure; Drug Design; Acrolein; Cell Division; Anti-Bacterial Agents; 3. Good health

In an attempt to discover potential antibacterial agents against the increasing bacterial resistance, novel cinnamaldehyde derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method, and their cell division inhibitory activity against four representative strains. In the in vitro antibacterial activity, the newly synthesized compounds generally displayed better efficacy against Staphylococcus aureus ATCC25923 than the others. In particular, compounds 3, 8 and 10 exerted superior or comparable activity to all the reference drugs. In the cell division inhibitory activity, all the compounds showed the same trend as their in vitro antibacterial activity, exhibiting better activity against S. aureus ATCC25923 than the other strains. Additionally, compounds 3, 6, 7 and 8 displayed potent cell division inhibitory activity with an MIC value of below 1 μg/mL, over 256-fold better than all the reference drugs.