The effects of novel heme oxygenase inhibitors on the growth of Pseudomonas aeruginosa
2019
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.
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