title: Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus.
abstract: The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active againstStaphylococcus aureus. Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting theMycobacterium tuberculosisthioredoxin reductase. This led to the discovery of a pyrazolone scaffold-containing compound series that showed bactericidal capability againstS. aureusstrains, including drug-resistant clinical isolates. The findings support continued development of the pyrazolone compounds as potential anti-S. aureusantibiotics.
authors.affiliation: Department of Pharmaceutical Sciences, Concordia University Wisconsin, 12800 N Lake Shore Dr, Mequon, WI 53097, USA. noreena.sweeney@cuw.edu.
authors.forename: Noreena L
authors.initials: NL
authors.lastname: Sweeney
authors.affiliation: Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA. lipker.laur@uwlax.edu.
authors.forename: Lauren
authors.initials: L
authors.lastname: Lipker
authors.affiliation: Department of Pharmaceutical Sciences, Concordia University Wisconsin, 12800 N Lake Shore Dr, Mequon, WI 53097, USA. alicia.schultz@cuw.edu.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Hanson
authors.affiliation: Department of Pharmaceutical Sciences, Concordia University Wisconsin, 12800 N Lake Shore Dr, Mequon, WI 53097, USA. chris.bohl@cuw.edu.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Bohl
authors.affiliation: Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA. katieengel92@gmail.com.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Engel
authors.affiliation: Department of Biochemistry, Medical College of Wisconsin, Wauwatosa, WI 53226, USA. kekalous@mcw.edu.
authors.forename: Kelsey S
authors.initials: KS
authors.lastname: Kalous
authors.affiliation: Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA. stemper.mary@marshfieldclinic.org.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Stemper
authors.affiliation: Department of Pharmaceutical Sciences, Concordia University Wisconsin, 12800 N Lake Shore Dr, Mequon, WI 53097, USA. Daniel.Sem@cuw.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Sem
authors.affiliation: Department of Microbiology, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA. wschwan@uwlax.edu.
authors.forename: William R
authors.initials: WR
authors.lastname: Schwan
keywords: MRSA; antibiotic target; enzyme inhibitor; molecular docking; pyrazolones; thioredoxin reductase