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

Abstract 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  μ M, 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.