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Pseudomonas aeruginosa is a common opportunistic pathogen that is responsible for nearly 10% of hospital-acquired infections. P. aeruginosa infections have become increasingly difficult to treat due to rising antibiotic resistance; thus, novel methods of treatment must be developed to combat infection. P. aeruginosa releases pyochelin to acquire nutrients and disrupt host biological processes. Pyochelin-deficient strains of P. aeruginosa demonstrated significantly lower growth ability and virulence. Because of pyochelin’s role in virulence and the unique proteins involved in secretion, the pyochelin biosynthetic pathway is an effective drug target for P. aeruginosa treatment. Before pyochelin is released, the precursor molecule is methylated by the PchF methyltransferase. We synthesized a PchF inhibitor which is expected to block methyltransferase activity, preventing pyochelin release. This inhibitor would effectively treat infections of P. aeruginosa and other iron-chelating bacteria, leading to new pharmaceuticals that can treat bacterial infection without the concern of antibiotic resistance.



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Design and Synthesis of Methyltransferase Inhibitors to Treat Pseudomonas aeruginosa Infections