Antimicrobial activity of various 4- and 5-substituted 1-phenylnaphthalenes

Bacterial cell division occurs in conjunction with the formation of a cytokinetic Z-ring structure comprised of FtsZ subunits. Agents that can disrupt Z-ring formation have the potential, through this unique mechanism, to be effective against several of the newly emerging multi-drug resistant strains of infectious bacteria. 1- and 12-Aryl substituted benzo[c]phenanthridines have been identified as antibacterial agents that could exert their activity by disruption of Z-ring formation. Substituted 4- and 5-amino-1-phenylnaphthalenes represent substructures within the pharmacophore of these benzo[c]phenanthridines. Several 4- and 5-substituted 1-phenylnaphthalenes were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis. The impact of select compounds on the polymerization dynamics of S. aureus FtsZ was also assessed.

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► FtsZ-targeting antibiotics disrupt formation of an essential cytokinetic Z-ring polymeric structure.
► 4- and 5-Amino-1-phenylnaphthalenes are substructures of compounds known to target FtsZ.
► Basic functional groups at the 4- and 5-positions of 1-phenylnaphthalene are associated with antibiotic activity.
► Several compounds have MICs that range from 0.5–1.0 to 2.0–4.0 ug/mL against MSSA and MRSA.
► Our data suggest antibacterial activity is associated with a stimulation of FtsZ self-polymerization.