Abstract
A novel series of FtsZ-targeted phenylacrylamides were designed, synthesized and evaluated for their antibacterial activity and cell division inhibitory activity against various Gram-positive and -negative strains. Among them, some compounds displayed preferable or comparable antibacterial activity and cell division inhibitory activity in comparison with their parent cinnamic acid. In particular, the compounds bearing 2-methylbenzimidazolyl groups showed more potent antibacterial activity than the others against the tested strains. For instance, compound 12 exhibited over 32-fold more potent antibacterial activity than cinnamic acid against Staphylococcus epidermidis and compound 16 exerted over 32-fold better antibacterial activity against Staphylococcus aureus ATCC25923 and S. epidermidis than cinnamic acid. In contrast, against Bacillus subtilis ATCC9372, Escherichia coli ATCC25922 and Pseudomonas aeruginosa ATCC27853, the phenylacrylamides showed little or no antibacterial activity. In the cell division inhibitory activity, compounds 14-17 displayed more significant on-target activity against S. aureus ATCC25923 than the other tested strains. In particular, the most active compound 14 shared the minimum cell division concentration of 0.5 µg/mL, which had over 256-fold better activity than all the references.
Keywords: 2-methylbenzimidazolyl group, antibacterial activity, cell division inhibitory activity, FtsZ, phenylacrylamides, synthesis.
Graphical Abstract
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