The effects of novel heme oxygenase inhibitors on the growth of Pseudomonas aeruginosa.

Objectives: This study was aimed to develop small molecule inhibitors of the P. aeruginosa heme oxygenase (pa-HemO) as potential treatment of infections caused by P. aeruginosa.
Methods: New compounds were designed based on the crystal structure of pa-HemO. The binding affinities (K _D ) were determined using intrinsic fluorescence quenching assays. The anti-microbial effects of the new compounds was evaluated by minimal inhibitory concentration 50% (MIC ₅₀ ).
Results: Eleven compounds were synthesized as potential pa-HemO inhibitors. New compounds demonstrated K _D values ranging from 1.5 to 180 μM, and MIC ₅₀ values ranging from 26 to 260 μg/mL. The compounds had good affinity with HemO and promising anti-microbial effects on P. aeruginosa.
Conclusions: The new inhibitors described herein can inhibit the growth of P. aeruginosa via the inhibition of pa-HemO. There may be broad prospects for HemO inhibitors to treat P. aeruginosa related infections.
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