A series of analogs of 2-tosylnaphthalene-1,4-diol were prepared and were found to be potent 10-20 nM reversible inhibitors of the Escherichia coli FabH enzyme. The inhibitors were also effective but to a lesser degree (30 nM-5 microM), against the Mycobacterium tuberculosis and Plasmodium falciparum FabH enzymes. Preliminary SAR studies demonstrated that the sulfonyl group and naphthalene-1,4 diol were required for activity against all enzymes but the toluene portion could be significantly altered and leads to either modest increases or decreases in activity against the three enzymes. The in vitro activity of the analogs against E. coli FabH parallel the in vivo activity against E. coli TolC strain and many of the compounds were also shown to have antimalarial activity against P. falciparum.