title: Syntheses and Biological Evaluations of Highly Functionalized Hydroxamate Containing andN-Methylthio Monobactams as Anti-Tuberculosis and β-Lactamase Inhibitory Agents.
abstract: Both the resurgence of tuberculosis (TB) and antibiotic resistance continue to threaten modern healthcare and new means of combating pathogenic bacterial infections are needed. The syntheses of monobactams possessing hydroxamate andN-methylthio functionality are described, as well as their anti-TB,in vitroβ-lactamase inhibitory, and general antimicrobial evaluations. A number of compounds exhibited significant anti-TB and β-lactamase inhibitory activity, with MIC values in the range of 25 to < 0.19μM againstMycobacteria tuberculosis (M.tb), and Kivalues in the range of 25-0.03 μM against purified NDM-1 and VIM-1 lystate metallo β-lactamases. This work suggests that these scaffolds may serve as promising leads in developing new antibiotics and/or β-lactamase inhibitors.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Majewski
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Watson
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, MIC 964, Rm. 412, University of Illinois at Chicago, IL, 60612, USA.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Miller
authors.affiliation: Institute for Tuberculosis Research, College of Pharmacy, MIC 964, Rm. 412, University of Illinois at Chicago, IL, 60612, USA.
authors.forename: Scott G
authors.initials: SG
authors.lastname: Franzblau
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, 46556, USA.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Miller