title: 1,2,4-Triazolidine-3-thiones as Narrow Spectrum Antibiotics against Multidrug-ResistantAcinetobacter baumannii.
abstract: With only two new classes of antibiotics developed in the last 40 years, novel antibiotics are desperately needed to combat the growing problem of multidrug-resistant and extensively drug resistant bacteria, particularly Gram-negative bacteria. Described in this letter is the synthesis and antibiotic activity of 1,2,4-triazolidine-3-thiones as narrow spectrum antibiotics. Optimization of the 1,2,4-triazolidine-3-thione scaffold identified a small molecule with potent antibiotic activity against multiple strains of multidrug-resistant and extensively drug-resistantAcinetobacter baumannii. This small molecule also shows single dose,in vivoactivity in aGalleria mellonellainfection model withA. baumanniiand represents a promising start in the development of a class of drugs that can target this bacterial pathogen.
authors.affiliation: Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.
authors.forename: William M
authors.initials: WM
authors.lastname: Huggins
authors.affiliation: Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.
authors.forename: Bradley M
authors.initials: BM
authors.lastname: Minrovic
authors.affiliation: Wound Infections Department, Walter Reed Army Institute of Research , Silver Spring, Maryland 20910, United States.
authors.forename: Brendan W
authors.initials: BW
authors.lastname: Corey
authors.affiliation: Wound Infections Department, Walter Reed Army Institute of Research , Silver Spring, Maryland 20910, United States.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Jacobs
authors.affiliation: Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.
authors.forename: Roberta J
authors.initials: RJ
authors.lastname: Melander
authors.affiliation: Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Sommer
authors.affiliation: Wound Infections Department, Walter Reed Army Institute of Research , Silver Spring, Maryland 20910, United States.
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Zurawski
authors.affiliation: Department of Chemistry, North Carolina State University , 2620 Yarbrough Drive, Raleigh, North Carolina 27695, United States.
authors.forename: Christian
authors.initials: C
authors.lastname: Melander
keywords: Acinetobacter baumannii; antibiotic resistance; antibiotics